It renews a competitive continental rivalry that has spanned decades.
Here, Press Association Sport looks at five of the best recent European meetings between the two giants.
Manchester United 3 Barcelona 0 (21/03/1984)
In the days before the Champions League and while Liverpool were busy dominating the European Cup, Manchester United were a top team in England but succumbed to a 2-0 Cup Winners' Cup quarter-final first-leg defeat by Barca at the Nou Camp, thanks to a Graeme Hogg own goal and Juan Carlos Rojo's late strike. However, back at Old Trafford, United pulled off a remarkable comeback against a team featuring Diego Maradona. Home captain Bryan Robson inspired the Red Devils with a diving header to open the scoring before making it 2-0 with a powerful finish from close range. Frank Stapleton fired home United's third from a Norman Whiteside lay-off and Ron Atkinson's men were able to celebrate a famous European triumph.
Manchester United 3 Barcelona 3 (16/09/1998)
Manchester United's 1998-99 Champions League campaign was inextricably linked to Barcelona. They were again paired in the group stages and the first game at Old Trafford was a thrilling affair. Early goals from Ryan Giggs and Paul Scholes put Sir Alex Ferguson's side 2-0 up at half-time before replies from Sonny Anderson and Giovanni levelled the game before the hour. David Beckham quickly restored United's lead but after Nicky Butt was dismissed for a foul which gave Barca a penalty, Luis Enrique converted from the spot.
Barcelona 3 Manchester United 3 (25/11/1998)
The return match at the Nou Camp was another topsy-turvy game that Barcelona needed to win to enhance their chances of getting through. Anderson gave them a flying start but Dwight Yorke levelled before half-time. Andrew Cole put United ahead before Rivaldo then scored either side of another Yorke goal as it ended 3-3 again. United would return to the Nou Camp later on in the tournament as they beat Bayern Munich in a memorable final to win the treble.
Manchester United 1 Barcelona 0 (29/04/2008)
It had been the best part of two years since the two sides had met, but they were paired in the semi-final in 2008. After United had emerged from the Nou Camp with a goalless draw, it was in their hands at Old Trafford and they went ahead early on from a wonderful Scholes goal. The midfielder unleashed a swerving shot from distance and that proved enough as Ferguson's side went through to the final in Moscow, where they beat Chelsea on penalties.
Barcelona 3 Manchester United 1 (28/05/2011)
Wembley was the venue for the second Champions League final between Barca and United in three years, after the Spanish side had won in Rome in 2009. Pedro put the Spanish side, who were at the height of their powers under Pep Guardiola, ahead but Wayne Rooney levelled before the break with a superb goal. United would have been dreaming of an emotional win on home soil, but a Lionel Messi-inspired Barca stepped it up and won it in the second half through Messi and David Villa goals.