Manchester United maintained their 15-point advantage at the top of the table to move closer to securing the title, while Wigan climbed out of the relegation zone and Chelsea lost to Southampton.
Sir Alex Ferguson's side look set to become champions once again after seeing off Sunderland in the day's early kick-off, although Manchester City responded impressively with a convincing win over Newcastle United.
The battle for UEFA Champions League qualification does look set to go down to the wire as Chelsea suffered a shock defeat and Tottenham Hotspur took advantage with a win over Swansea City to go third.
Arsenal are just two points adrift of a spot in the top four after demolishing Reading to leave Nigel Adkins' new side bottom of the table, with Aston Villa and QPR now joining them in the relegation places after a vital win for Wigan Athletic against Norwich City.
Elsewhere, Everton edged out Stoke City to stay in touch with the European chase and West Ham United prevailed against West Bromwich Albion.
Manchester United temporarily moved 18 points clear at the summit after a narrow 1-0 victory at the Stadium of Light, to leave Sunderland hovering precariously above the drop zone.
The crucial goal arrived in the 27th minute when Robin van Persie's fierce strike from a tight angle took a deflection off Titus Bramble and flew past Simon Mignolet.
United suffered late heartbreak on Wearside on the final day of last season as Manchester City snatched the title in dramatic style, but on this occasion there was to be no final twist as Sunderland rarely threatened to grab an equaliser.
Manchester City manager Roberto Mancini has already conceded defeat in this year's title race but has demanded a strong finish from his side, and they were far too strong for Newcastle in a 4-0 home win at the Etihad Stadium.
It was a frustrating start for City as Gareth Barry missed a glorious chance and a goal was disallowed, but the pressure eventually paid off as Carlos Tevez turned in a Gael Clichy cross in the 41st minute.
City made it 2-0 on the stroke of half-time after some great play to work their way through a crowded area, with David Silva firing home a low finish after being played in by Samir Nasri.
Vincent Kompany, back in the side following his controversial appearance for Belgium after injury, cheekily flicked in a Barry strike to add a third, and James Perch's own goal completed the scoring as City tightened their grip on second place and left Newcastle looking over shoulders.
If Adkins did not already know the size of the task facing him to lead Reading to safety, it became apparent on a tough day at the Emirates Stadium as Arsenal ran out 4-1 winners to boost their hopes of breaking into the top four.
Gervinho broke the deadlock from close range in the 11th minute after a cross-shot from Santi Cazorla, and it could have been more for the Gunners by half-time as Reading were subjected to an onslaught from the hosts.
Cazorla did add a second immediately after the restart with a neat strike into the bottom corner, before Olivier Giroud rifled in a third following a swift counter-attack.
Hal Robson-Kanu headed in a Jobi McAnuff cross to briefly reduce Reading's arrears, but Mikel Arteta slotted in a penalty to put the gloss on Arsenal's afternoon after Alex Oxlade-Chamberlain had been brought down by Adrian Mariappa.
Southampton eased their relegation worries with an enthralling 2-1 victory over Chelsea which dents the Blues' chances of clinching a Champions League place.
Chelsea manager Rafael Benitez shuffled his pack at the start of a gruelling period of eight games in 23 days, but they were soon trailing as Jay Rodriguez coolly slotted home for Southampton after receiving Steven Davis' pass at the end of a flowing move.
John Terry, making just his second Premier League start under Benitez, equalised with a free header from a corner on 33 minutes, but Rickie Lambert restored Southampton's lead two minutes later with a sublime curling free-kick.
Tottenham bounced back from a couple of dispiriting defeats prior to the international break to beat Swansea 2-1 at the Liberty Stadium and climb back above Chelsea into third place.
Belgian defender Jan Vertonghen provided another demonstration of his attacking capabilities with a goal that would have made any centre-forward proud, rushing into the box to beautifully control a Gareth Bale pass and then calmly tuck the ball home to give Spurs a seventh-minute lead.
The same two players combined for Tottenham's second on 21 minutes as Vertonghen picked out Bale 20 yards from goal and the Welshman nonchalantly poked an extraordinary finish into the top corner to take his Premier League tally for the season to 17.
Michu pulled a goal back for Swansea with a header from a corner to set up a tense finale, but Spurs held on to go two points clear of Chelsea and retain their four-point lead over fifth-placed Arsenal.
Out of the drop zone
Wigan moved out of the bottom three courtesy of a hard-fought 1-0 victory over Norwich at the DW Stadium.
Both sides struggled to carve out chances in an uninspiring first half but the game came to life after the interval and Arouna Kone emerged as the match-winner for the Latics as he beat Lee Camp at his near post with nine minutes remaining.
West Ham strengthened their position in mid-table with a 3-1 triumph at home to West Brom which should dispel any lingering fears of relegation.
Andy Carroll responded emphatically to a challenge from manager Sam Allardyce for more goals from his strikers with a powerful header from a corner in the 16th minute, and Gary O'Neil doubled West Ham's advantage just before the half-hour mark thanks to a fabulous effort from outside the area which dipped over Ben Foster.
Carroll netted his second of the game ten minutes from time with a skilful first-time volley as he watched the ball carefully over his shoulder before swivelling to send the ball into the net.
Graham Dorrans' late penalty was a mere consolation for the Baggies, who also had Youssouf Mulumbu sent off in the dying seconds.
In the final game of the day, Everton kept their bid for a top-four spot alive with a 1-0 victory over Stoke at Goodison Park.
It was a superb solo goal that proved to be the difference between the sides as Kevin Mirallas ran from inside his own half before firing past Asmir Begovic in the 28th minute.
The result keeps Everton in sixth, just two points behind Arsenal and now six ahead of Liverpool, while Stoke are in danger of being sucked into the relegation scrap after a fifth game without a win.