Nigel Adkins's tenure as manager of promotion favourites Sheffield United began with a surprise 4-0 defeat at Gillingham.
The Blades were tipped to challenge for the League One title this season, thanks to the appointment of Adkins as well as some eye-catching signings, but came unstuck as Gillingham struck in the first half through on-loan Spurs forward Emmanuel Osadebe and Adedeji Oshilaja. John Egan and Bradley Dack completed the scoring late on.
Fellow promotion contenders Wigan Athletic, relegated from the Championship last season, similarly struggled as they lost 2-0 at Coventry City.
Adam Armstrong, on loan from Newcastle United, bagged his first senior goal in the first half, and then doubled his career tally with his second after the break.
A Nathan Byrne hat-trick and Lawrence Vigouroux penalty save inspired Swindon Town to a 4-1 victory over Bradford City.
Josh Morris gave the Bantams the lead after only four minutes, and they could have doubled their lead only for Vigouroux to keep out Billy Clarke's spot kick.
The game completely turned on its head in the second half as Byrne scored a 16-minute treble, before Jonathan Obika added a fourth.
Former Premier League midfielder Darren Ambrose marked his Colchester United debut with his first league goal in three years to salvage a 2-2 draw with Blackpool.
Mark Cullen gave the Seasiders a 2-1 half-time lead after he struck either side of Alex Gilbey's leveller for the U's.
Three second-half goals saw Chesterfield overturn a 1-0 half-time deficit to record a 3-1 win over Barnsley.
Much is expected of Lee Johnson's young Reds team this season and they scored early on through Conor Wilkinson, but Jay O'Shea equalised just after the break and then Sylvain Ebanks-Blake and Sam Morsy struck a minute apart of each other to secure the victory.
There were bizarre scenes at the Keepmoat Stadium where Doncaster Rovers drew 1-1 with Bury.
Doncaster took a late lead as the ball found its way into the back of the net when Harry Forrester was returning it to the Bury goalkeeper, but manager Paul Dickov instructed his side to allow Leon Clarke to equalise unopposed.
Millwall won 2-1 at Shrewsbury Town, with striker Steve Morison notching on his first start of a third spell at the club.
James Collins put Shrewsbury ahead on 55 minutes, before Morison equalised and Lee Gregory converted a penalty to win the game.
Scunthorpe United goalkeeper Luke Daniels saw red as the Irons were beaten 2-1 at Burton Albion.
Stuart Beavon and a Lucas Atkins penalty, which was awarded in the incident in which saw Daniels sent off, gave Albion a two-goal cushion which proved vital as Charlie Goode pulled one back late on.
Jonathan Forte's late goal salvaged Oldham Athletic a 1-1 draw at Walsall, who took an early lead through Romaine Sawyers's strike.
Fleetwood Town and Southend United also drew 1-1, as David Worrall struck late on to cancel out Dean McManus's Fleetwood opener.
Rochdale beat Peterborough United 1-0 thanks to a Callum Camps goal, while Crewe Alexandra and Port Vale played out a goalless draw.
Results in full: Burton Albion 2-1 Scunthorpe United, Chesterfield 3-1 Barnsley, Colchester United 2-2 Blackpool, Coventry City 2-1 Wigan Athletic, Crewe Alexandra 0-0 Port Vale, Doncaster Rovers 1-1 Bury, Fleetwood Town 1-1 Southend United, Gillingham 4-0 Sheffield United, Rochdale 1-0 Peterborough United, Shrewsbury Town 1-2 Millwall, Swindon Town 4-1 Bradford City, Walsall 1-1 Oldham Athletic.