Liverpool smashed six goals at Newcastle to add to the hosts' relegation concerns, while Wigan were denied victory over Tottenham due to a late own goal from Emmerson Boyce, and Manchester City comfortably defeated West Ham to move closer to clinching second in the Premier League.
Elsewhere, Stoke aided their own survival quest immensely with a home win over Norwich, as Everton defeated Fulham at Goodison Park and West Brom thrashed Southampton in a game that saw three players sent off.
Liverpool made light of Luis Suarez's absence as they thrashed Newcastle United 6-0 at St James' Park, with the Magpies now just five points clear of the drop zone.
Daniel Agger set the tone when heading Liverpool ahead inside four minutes. The excellent Philippe Coutinho and Daniel Sturridge combined to tee up Jordan Henderson for the second.
A brief Newcastle rally was snuffed out when Coutinho created the third for Sturridge, and the England forward added a fourth shortly afterwards.
Fabio Borini climbed off the bench to net his first Premier League goal 16 minutes from time, and salt was rubbed into the wounds when former Sunderland star Henderson netted the sixth.
A late, painful own goal from Emmerson Boyce could prove decisive for Wigan at the end of the season, as it ensured they drew 2-2 with Tottenham in a result that hardly helped the Londoners' Champions League ambitions.
Callum McManaman's impressive strike had looked like clinching all three points for the Latics and propelling them out of the bottom three, but Boyce got his feet in a tangle while trying to deal with an 89th-minute cross to hand the visitors a late share of the points.
That prevented Wigan climbing out of the relegation zone, instead leaving them two points from Aston Villa in 17th, while it limited the damage to Spurs' own Champions League pursuit - although Andre Villas-Boas will now need results to go his way if Spurs are to end up in fourth.
In the day's early kick-off, Manchester City went a long way towards confirming a second-place finish in the table with a 2-1 victory over West Ham that was more comfortable than the final scoreline ultimately suggests.
Sergio Aguero, restored to the starting lineup, opened the scoring on the half-hour mark, turning home from Samir Nasri's cutback after a sublime team passing move. Yaya Toure then doubled the advantage with a long-range strike, before Joe Hart fumbled an Andy Carroll volley deep into injury time to give the Hammers a belated consolation.
The result means seven points from their final four games will guarantee City finish the season in second. West Ham, meanwhile, remain safely in mid-table.
Everton's hopes of European qualification remain alive after they edged a lacklustre Fulham 1-0 at Goodison Park.
Steven Pienaar got the only goal of the game for the Toffees, who are now just three points behind Spurs in fifth having played a game more.
Fulham were hampered by the loss of Dimitar Berbatov, who was forced off through injury shortly before the half-hour mark. They were already behind by that point, though, with Steven Pienaar blasting home from inside the box after latching onto Seamus Coleman's slipped pass.
Everton peppered the Cottagers' goal over the remainder of the match - compiling 20 shots to Fulham's five - but just three of those were on target, with Victor Anichebe, Nikica Jelavic and Marouane Fellaini perhaps guilty of the most egregious misses.
Hugo Rodallega then had a late opportunity to punish the home side for their wastefulness, but the forward headed wide from Damien Duff's cross to ensure Martin Jol's side would not get a draw they did not warrant.
Wigan's late woe was a boon for Stoke, who now enjoy an eight-point cushion over the bottom three after defeating Norwich - two points worse off - 1-0 at the Britannia Stadium.
Charlie Adam broke the deadlock shortly after half-time, the Scotland international running onto Peter Crouch's knockdown and sweeping a left-footed finish beyond Mark Bunn.
Finally, West Brom look almost certain to finish in the top ten after defeating Southampton 3-0 at St Mary's in a game that saw three red cards.
Goals from forwards Marc-Antoine Fortune, Romelu Lukaku and Shane Long were the difference for Steve Clarke's side, as the Saints saw their own top-half ambitions dented somewhat. The game was marred slightly by an unsightly second-half incident that saw both Gaston Ramirez and Fortune shown straight red cards, however.
It took just six minutes for Fortune to break the deadlock, the striker bundling home from close range after Ben Foster had initially made a good save, and Lukaku grabbed a second with 23 minutes remaining after running onto Fortune's throughball and evading Jos Hooiveld.
That was about Fortune's last contribution of the game, as he was then sent off after slapping Ramirez - having reacted angrily to the Argentine's elbow on Long, an offence for which he was also dismissed by referee Robert Madley.
Madley's work was far from done, however, as he was forced to react once again minutes later, dismissing Daniel Fox for a dangerous tackle on Steven Reid. Long then added his name to the scoresheet, rounding off a comprehensive victory for the visitors after gratefully taking an assist from the lively Lukaku.