Wigan stunned 10-man Chelsea at the DW Stadium as Manchester United edged back to the summit thanks to their victory over Stoke.
Fernando Torres hit a hat-trick as Liverpool trounced troubled Hull City at Anfield, while Merseyside neighbours Everton handed pointless Portsmouth their seventh successive defeat.
Tottenham proved far too strong for poor travellers Burnley at White Hart Lane as Robbie Keane scored four, Arsenal won at Fulham, while Bolton edged past Birmingham at St Andrews and 10-man Blackburn grabbed the points against Aston Villa with a late penalty.
Chelsea's 100 per cent start to the Premier League season was brought to a shuddering halt as Wigan finally tasted victory over one of the so-called 'Big Four' at the 35th time of asking.
Titus Bramble headed the hosts into an early lead as he was left unmarked in the box only for Didier Drogba to respond at the start of the second period.
But the Blues were reduced to 10 men with Petr Cech seeing red for felling Hugo Rodallega as he raced through, with the Latics forward picking himself up to beat replacement Hilario from the spot.
With Ashley Cole off the field injured, Wigan completed the scoring in the closing moments to secure a memorable 3-1 success with Paul Scharner scoring from virtually on the line.
SummitManchester United are back at the summit of the Premier League on goal difference after their 2-0 success away to Stoke City, with Ryan Giggs stepping off the bench to inspire the Red Devils.
Giggs was released by Darren Fletcher before crossing for Dimitar Berbatov to tap home the opener in the 62nd minute before curling in a superb free-kick which John O'Shea glanced home.
Fernando Torres scored a sublime hat-trick as Liverpool trounced troubled Hull City 6-1, banishing the memory of their home draw with the Tigers last term.
The Spain international demonstrated his lethal prowess in front of goal, completing his treble early in the second half as the visiting defence simply could not cope with his pace and trickery.
Geovanni had briefly silenced Anfield with a 15th-minute leveller before Torres took charge, with Steven Gerrard's screamer and Ryan Babel's late brace completing the rout to increase the pressure on Phil Brown.
Robin van Persie's second-half goal allowed Arsenal to keep pace with the leaders after a 1-0 win at Fulham.
Dutch striker Van Persie produced a cool finish on 52 minutes, but the Gunners were indebted to Vito Mannone for the points after the rookie keeper pulled off a string of fine saves.
Portsmouth suffered a seventh successive Premier League defeat as they were beaten 1-0 by Everton at Fratton Park despite producing a much-improved display.
Louis Saha scored the only goal of the game as he seized on an error by Younes Kaboul to fire beyond David James. Pompey hit back after the break and went desperately close on three occasions but could not find a way beyond Tim Howard.
Four-goal haulRobbie Keane helped himself to a four-goal haul to get Tottenham back to winning ways as Burnley's away struggles in the Premier League continued with a 5-0 drubbing at White Hart Lane.
The Republic of Ireland striker opened his account from the spot after Jermain Defoe was brought down before adding three more after the interval, with Jermaine Jenas' deflected effort adding to the Clarets' woes.
Bolton substitute Lee Chung-Yong was the hero for Gary Megson's men as he snatched a late winner from their trip to Birmingham.
Tamir Cohen headed the visitors in front after just 10 minutes before Kevin Phillips levelled after Lee's error, only for the South Korean to immediately make amends at the other end of the field.
Blackburn climbed out of the bottom three courtesy of David Dunn's late penalty against Aston Villa, despite Vince Grella seeing red earlier in the afternoon.
Gabriel Agbonlahor gave the visitors the perfect start with just three minutes on the clock before Chris Samba out-muscled Richard Dunne to equalise before the break.
Dunne was then harshly penalised by referee Mark Clattenburg as he blocked a shot from point-blank range with his hands raised above his head, but Dunn made no mistake to beat former Ewood Park favourite Brad Friedel from 12 yards.