However, the five-time champion saw her 34-match unbeaten record ended in spectacular fashion by Germany's Lisicki.
Read how another huge upset at this year's Championships unfolded below.
12.30pmHello folks. The second Monday at Wimbledon is always one of the best days on offer to fans and this year it's no different.
12.32pmOn court today we have the two women involved here as well as Andy Murray, Novak Djokovic, David Ferrer, Laura Robson, Juan Martin del Potro, Petra Kvitova and much more. What a treat!
12.33pmA true tennis feast and here on SM we're of course covering many of the games.
12.35pmAlready we have commentaries going for Ferrer and Kvitova, while Laura Robson's match is first on No. 1 Court and our coverage of that will be on site shortly. I'll let you know when.
12.39pmSo far today Kvitova took the first set on a tie-break and men's fourth seed Ferrer is now also in one for the first set against Ivan Dodig. Follow the breaker with Matt Domm here.
12.43pmWHO? Those who don't really follow tennis but love it when Wimbledon comes around will recognise the name of Lisicki. She is a 23-year-old German who loves the All England grass - she's never got past the fourth round of another Slam. In the last two years she's reached the semi-finals and quarter-finals respectively.
12.46pmAnother favourable stat for Lisicki is that in three of the last four years she has knocked out the reigning French Open champion from the previous month. In 2009 it was Svetlana Kuznetsova, 2011 Maria Sharapova and 2012 Li Na. This year it's Serena but a victory for the German today would be the biggest of her career.
12.50pmIf you do fancy Lisicki to cause a major upset and end Serena's 34-match winning streak, she's anywhere from eight to 11/1 with the bookies.
12.53pmUpset on the cards? Dodig snatches the first set against Ferrer in the tie-break. Could another top seed be on their way? Ferrer was the better player in the set but failed to convert on EIGHT break points. Follow the remainder here.
12.58pmOur updates for Robson's match against Kanepi over on No. 1 Court are now live with Liam Power. I'd right-click here and open in a new tab ;)
1.01pmWilliams and Lisicki walk out to a warm reception on Centre as Petra Kvitova becomes the first person to reach the quarter-finals this year. She defeats Carla Suarez-Navarro 7-6 6-3 over on No. 3 Court.
1.05pmH2H: These two have met just twice and Williams has won both. However, they were both on the hard courts of America and Lisicki is a different animal on the grass.
1.08pmThe German will without doubt be the crowd favourite this afternoon. Not only do they always love an underdog but Lisicki's performances at SW19 over the last four years have made her a darling of the All England Club.
1.10pmAs always, there's a host of famous faces in the Royal Box. On one day last week cricket was the dominant sport but today it's golf. The legendary Jack Nicklaus is there, Ernie Els and Ian Poulter too.
1.12pmUmpire James Keothavong announces that Lisicki won the toss and chose to serve. Here we go...
1.13pmFirst point to Lisicki as she blasts down a first serve that Williams swipes well out on the forehand.
1.14pmBullish from the American on the next point as she approaches the net and swats a drive-volley right onto the baseline.
1.15pmAt 30-15, Williams's return is mishit and lands just on the line. Lisicki stops the point to challenge but it's wrong and that could be costly.
1.15pmBREAK POINT to Serena as she lashes a backhand return that Lisicki can't reach.
1.16pmBrilliantly saved by Lisicki, producing a good second serve and then approaching the net successfully.
1.17pmLisicki now has a chance to hold serve but she double faults and we're back to deuce.
Williams *0-1 LisickiSuperb way to hold! Serena does well to get back a big Lisicki serve and her return just dips over the net. Lisicki has to go for broke and finds the corner with a down-the-line backhand.
1.18pmLisicki with a brutal return to start Williams's first service game. The American gets it back though and Lisicki tries a drop shot but gets it horribly wrong.
Williams 1-1* LisickiA love hold for Williams, but there were some encouraging signs for Lisicki there as she spurned two of the points with unforced errors.
1.22pmIt's looking dodgy for Lisicki at 15-30 but she stays in the rally well against Williams, who hooks a forehand wide after 13 strokes - the longest exchange of the match so far.
1.23pmA second double from Lisicki and it's another BREAK POINT for Williams.
1.23pmSaved again by the German! Serena's return is good but Lisicki doesn't give up and Williams nets a backhand.
1.24pmWilliams with a third break-point opportunity but again it goes begging as Lisicki powers an in-to-out forehand right into the corner.
Williams *1-2 LisickiBig, big hold for Lisicki. She's already saved three break points and is having to work so hard to stay in this. So hard in fact that she's had to remove her skin-tight long-sleeve sweater thing.
1.30pmYou don't often see this but Lisicki is matching Williams from the baseline at the moment. Unfortunately for the German she is making many more unforced errors, five to Serena's one.
1.31pmShe has got an excellent forehand though and two winners off that wing bring us back to deuce on the Williams serve.
1.32pmA big serve at deuce sparks a "Come On!" from Serena but she then FOOT FAULTS at advantage before hitting a backhand long. Back to deuce.
1.33pmAnother game-point chance goes as Lisicki continues to not hold back from the baseline.
1.34pmWilliams stops the point because she thinks Lisicki's return is long but it was a brilliant one that just caught the baseline. Back to deuce again and the time of this game is approaching seven minutes.
1.34pmBREAK POINT Lisicki as she wrongfoots Serena with another forehand winner...
1.35pmKicking serve out wide saves it for Williams.
1.36pmBack to deuce again! Lisicki is really playing well here.
Williams 2-2* LisickiAlmost 10 minutes that game took. Serena comes through with two mighty serves and this match is on course to be a cracker.
1.40pmLisicki has two chances to close out the game but squanders both and we're back at deuce.
1.42pmLisicki wastes two more opportunities to hold serve. She has to take these sort of chances to have any hope of upsetting the number one seed.
1.44pmWilliams has a chance to break but doesn't do enough with the second-serve return and Lisicki puts away another forehand winner.
1.45pmWe've had so many deuces so far in this game! Six in the last and we're already up to five in this Lisicki service game. Over half an hour played and we're only in the fifth game.
Williams *2-3 LisickiLisicki hit two second-serve ACES in that game. The second sees her hold serve and this truly is a brilliantly close match. Lisicki has hit 14 winners to Williams's five!
1.49pmTotal points won after the first five games? Serena 29-29 Sabine.
Williams 2-4* LisickiBREAK! Williams begins the game with her second and third aces but is soon 30-40 behind. She finds a big serve down the middle but somehow Lisicki lobs the ball high into the sky and inside the baseline. You'd expect the world number one to rocket the backhand away but she fluffs her lines and amazingly it's Lisicki who breaks first.
1.53pmLisicki moves to 40-0 but we're back to deuce AGAIN as the German misfires on a couple of forehands. This would be a killer blow if she fails to consolidate that break, especially being 40-0 ahead.
Williams *2-5 LisickiThe German does manage to hold serve though as Serena uncharacteristically dumps a pair of backhand returns into the net.
1.57pmDear me. Serena begins the next game with a limp 80mph double fault. Her first of the match.
Williams 2-6 0-0* LisickiSET! Wowee! Lisicki grabs the opening set by securing a double break to love. Williams looked like she'd completely given up in that game.
1.59pmOver on No. 1 Court it's heartbreak for British fans as Laura Robson loses the opener 8-6 in a tie-break after serving for the set at 5-4 and leading 5-2 in the breaker.
Williams 2-6 *0-1 LisickiYou'd expect Williams to come out all guns blazing at the start of the second but there's little she can do against the brilliance of Lisicki at the moment. The German wraps up a hold to 15 with her third second-serve ace. Great stuff.
Williams 2-6 1-1* LisickiThat's better from the American. She does what she did in the first set by holding to love with her first service game.
2.05pmAnd now Williams looks dangerous. She's 30-0 up on the Lisicki serve after a backhand winner and missed Lisicki forehand.
2.05pmTHREE BREAK POINTS for Serena as she swipes a forehand return down the line. "Get in," she mutters to herself.
Williams 2-6 *2-1 LisickiBREAK! The number one seed breaks at last as Lisicki hits long on the first. That was her fifth break point of the match and the first she's converted.
Williams 2-6 3-1* LisickiErrrm, that's now 12 points in a row for Williams as she again holds to love. What a turnaround.
2.10pmMake that 14 as Williams moves 0-30 ahead in the fifth game.
2.11pmLisicki finally ends the sequence, also finding a sublime backhand pass to bring it back to 30-30 before saving another break point at 30-40.
2.13pmA second break point of the game for Williams as she bullets a Lisicki first serve right back at the German before putting away an easy volley.
Williams 2-6 *4-1 LisickiDOUBLE BREAK! This set looks to be in the bag for Williams as Lisicki attempts a drop shot after a big serve but pulls it wide.
2.15pmOver on No. 3 Court sixth seed Li Na has just wiped the floor with 11th seed Roberta Vinci, seeing off the Italian 6-2 6-0 in under an hour.
2.20pmLisicki is getting the crowd back on her side in this game. It's almost certain that she's going to lose this set but she's not letting Williams have this game, saving several game points.
Williams 2-6 5-1* LisickiShe can't save another one and Williams is now within a game of levelling the match. The American hasn't made a single unforced error in this set.
2.23pmTHREE SET POINTS for Williams as she dominates the Lisicki serve.
Williams 2-6 6-1 *0-0 LisickiSET! Half an hour ago it looked like the number one seed would be on her way home but now she looks sure to reach the quarter-finals as expected.
2.25pmLisicki now needs to improve herself in a similar way to how Serena did after the first. She doesn't have the same game as the American though and will need to play just as well as she did in the first to have any chance of causing an upset.
Williams 2-6 6-1 1-0* LisickiComfortable hold to 15 for Williams to begin the decider. Lisicki now has to hold serve to steady herself. New balls in hand for the German.
2.33pmThe 23-year-old is looking good at 40-0 but goes for a wild forehand winner that is nowhere near. We're then back to deuce as Williams gets TWO extremely lucky net cords. That's incredible and the second time Lisicki has spurned a 40-0 lead on serve.
Williams 2-6 6-1 *2-0 LisickiBREAK! It's worst-case-scenario stuff for Lisicki as she hits wide with a forehand to gift Serena the break. It was ever so fortunate though for the top seed though because of those two dead net cords.
2.38pmEncouraging for Lisicki as she passes Serena with a cracking forehand. The American even applauds the ball as it flies past her.
Williams 2-6 6-1 3-0* LisickiWilliams double faults at 40-15 after being called for a foot fault but consolidates the break on the next as Lisicki hits out on the return.
2.43pmOver on No.1 Court Laura Robson has saved four match points! Can she break back in the second against Kanepi?
2.44pmNo, she can't. The British number one exits Wimbledon 7-6 7-5 and breaks into tears as she leaves the court.
Williams 2-6 6-1 *3-1 LisickiLisicki ends a run of nine straight games against her to get on the board in the third set.
2.48pmLisicki briefly apologises to Williams after a dead net cord of her own but then celebrates it because of those two Williams got earlier in the set. Such a likeable character.
2.49pmAnd now Lisicki is back to deuce as Williams fails to take two chances to close out the game.
2.50pmBREAK-BACK POINT for Lisicki as Serena nets a backhand.
Williams 2-6 6-1 3-2* LisickiBREAK BACK! She's done it! When Serena broke early in the set most would have expected the American to race away with it like she did in the second. However, Lisicki is a fighter and breaks back in the third thanks to Williams's pulled backhand.
2.52pmIt's so important that the German now moves back level in the decider by holding serve here.
2.55pmNervy moments for Lisicki at 30-30 now on her serve.
2.55pmAnd she plays a tame backhand barely halfway up the net and Williams has a chance to regain the break.
Williams 2-6 6-1 *4-2 LisickiBREAK! Which she does! Launching a forehand up the line that dips into the corner. Surely that's game over?
2.57pmLisicki won't go away easily though and is 0-30 up on the Williams serve.
2.58pmA sixth ace of the match for Serena ensures it doesn't go to 0-40. Lisicki challenged but it was well inside the box and the crowd have a little giggle at the German's bad judgement.
2.58pmTWO BREAK-BACK POINTS for Lisicki as Serena half-volleys wide...
Williams 2-6 6-1 4-3* LisickiBREAK BACK! This is great! It's three breaks of serve in a row as Lisicki manages it on the second. Serena came to the net but it was a weak approach and Lisicki hit a pass that Serena couldn't get down to.
3.01pmI said it last time Lisicki broke back and I'll say it again, she has to hold here.
3.01pmThe game doesn't begin well for the German as Serena nails a stunning return winner crosscourt with her forehand.
3.02pmNow 0-40 to Serena as she spanks another return winner, this time a backhand up the line. Sensational.
3.03pmLisicki saves the first two. One left...
3.03pmSo gutsy from the 23-year-old! She goes for it with a forehand from the baseline and the ball loops into the corner.
3.04pmLisicki has a chance to hold but goes to that drop shot again and it doesn't deliver. Back to deuce.
Williams 2-6 6-1 *4-4 LisickiThat is massive for Lisicki as she does manage to hold after being 0-40 down. She has all the momentum, can she break Williams again? She's done it the last two times.
3.07pmA big scream of encourage from Serena as Lisicki lets her off for a poor forehand. 30-15.
3.08pmIt's now 4-4, 30-30 as Williams approaches and can't put away the volley on the stretch from Lisicki's backhand pass.
3.09pmBREAK POINT Lisicki. Brilliant hitting from the German.
3.09pmThe crowd is definitely on Lisicki's side but she can't break as Serena finds a first serve and Lisicki nets.
3.10pmAnother break point for Lisicki as she makes Williams slip with a drop shot before beating the American at the net.
Williams 2-6 6-1 4-5* LisickiBREAK! Unbelievable! Williams rifles a backhand into the corner but somehow Lisicki gets her racket to it and lobs the ball up. It's just out of Serena's comfort zone and her smash on the reach goes just out! There's a bit of confusion as to whether it was called out and it was and Serena doesn't challenge. Lisicki will serve for the match!
3.14pmLisicki moves to 30-0 and is looking good but Williams shows great resolve to stay in the rally and pull it back to 30-15.
3.14pmStrong play again from Williams and we're back to 30-30. Nothing more than courteous applause from Centre Court. They want Lisicki to win.
3.15pmExcellent serve out-wide from Lisicki and it's MATCH POINT...
3.15pmAnother first serve but Williams with a superb deep return that Lisicki hits out.
3.16pmDOUBLE FAULT from Lisicki and it's break point Williams. So much tension!
3.16pmShe finds an ACE! Her tenth of the match and what a time just after that double.
3.17pmMatch point number two for Lisicki...
Williams 2-6 6-1 4-6 LisickiGAME, SET AND MATCH LISICKI!
3.18pmAnother mammoth upset at this year's Championships. Serena's unbeaten run ends at 34. The American congratulates her conquerer in lovely fashion at the net. If my lip reading is right then Serena told Sabine to go on and win the whole thing. Nice.
3.19pmSabine is almost in tears as she walks back out from her chair to huge applause from the Centre Court crowd.
3.21pmWhat odds could you have got on Serena, Sharapova, Federer and Nadal all being knocked out before the quarter-final stage? I dread to think.
3.22pmLisicki is being interviewed by BBC Sport and she breaks down in tears. There's not many Germans the British public love but this 23-year-old is definitely one of them.
3.24pmThat is the fourth time in a row that Lisicki has knocked out the reigning French Open champion.
3.24pmWhen asked what she thinks about her next opponent - Kaia Kanepi, who beat Laura Robson earlier - Lisicki says that she's not thinking about that yet.
3.26pmThanks for joining Sports Mole for coverage of this incredible match. Commentary for the next match on Centre involving Andy Murray will be live on site very shortly. See you there.