Manchester United have one hand on the Premier League trophy after their 1-0 victory over Reading at Old Trafford and Manchester City's 2-0 defeat by Everton at Goodison Park.
Queens Park Rangers suffered a damaging defeat away to Aston Villa in their battle to beat the drop with Paul Lambert's side claiming victory in a five-goal thriller.
Southampton halted Liverpool's recent charge to boost their own survival hopes, Arsenal edged out Swansea 2-0 at the Liberty Stadium, with Stoke's home meeting with West Brom ending in stalemate.
Manchester United now hold a surely insurmountable 15-point lead at the top of the Premier League table following their narrow, but routine, victory over Reading at Old Trafford.
Wayne Rooney scored the only goal of a low-key and largely one-sided game with a deflected effort from outside the box in the 21st minute to condemn the managerless Royals to their sixth successive top-flight defeat.
With just nine games remaining for Sir Alex Ferguson's side it will take a collapse of Devon Loch proportions to prevent them claiming their 20th top-flight crown.
Christian Benteke scored a priceless late winner for Aston Villa in a five-goal thriller against Queens Park Rangers to lift Paul Lambert's men six points clear of the drop zone and leave the rock-bottom visitors seven from safety.
The Rs forged ahead when Jermaine Jenas was gifted possession just inside the Villa half and he drove forward before releasing Bobby Zamora. The striker saw his shot saved by Brad Guzan, who had earlier made two superb stops from Chris Samba, but Jenas had continued his run and was on hand to tuck home the loose ball.
Villa were back on terms just before the interval as Matt Lowton's hanging cross had the QPR defence back-pedalling towards their own goal and, with Julio Cesar rooted to his line, Gabriel Agbonlahor was able to nod home from close range.
Villa Park erupted in the 59th minute as Andreas Weimann's superb turn and shot from the edge of the area saw his low drilled effort beat Cesar at his near post, only for Andros Townsend to level with a scrappy effort from distance.
And it was left to Benteke to have the final say in the 81st minute, with the powerful striker converting after Weimann's persistence had seen him burst into the box before pulling the ball back for his team-mate.
Everton delivered what will surely be a fatal blow to Manchester City's already fading Premier League title hopes with a 2-0 success at Goodison Park.
Leon Osman's long-range effort curled away from a static Joe Hart and into the top corner in the 32nd minute as the home side banished the memories of their limp FA Cup exit to Wigan last weekend.
Steven Pienaar was issued with a deserved red card following a late and high challenge on Javi Garcia in the 61st minute before City were denied a clear penalty when Marouane Fellaini handled Carlos Tevez's shot well inside the box, only for referee Lee Probert to award a free-kick outside the area.
With the visitors pressing for a late equaliser they were hit on the break in injury time as Fellaini burst away and released substitute Nikica Jelavic, who ended his goal drought with a deflected effort.
Liverpool's recent resurgence was brought to a shuddering halt with a 3-1 defeat at Southampton, who now have a seven-point cushion over the relegation zone.
Brendan Rodgers' side went into the game on the back of three successive Premier League victories, but fell 2-0 down inside 33 minutes after goals from Morgan Schneiderlin and Rickie Lambert.
Schneiderlin's deft touch from Jay Rodriguez's knockdown after Gaston Ramirez's cross went beyond Brad Jones, before the Liverpool keeper was beaten by Lambert's free-kick, which took a big deflection off the backside of Daniel Sturridge in the wall as he jumped and turned his back.
Sturridge then used his body to good effect at the right end of the field before seeing his shot blocked as Philippe Coutinho opened his account for the Reds to pull one back on the stroke of half-time.
But Liverpool's defence, and Martin Skrtel in particular, then allowed Rodriguez to advance unchecked into the area, with the Saints man converting at the second attempt after Jones' initial save.
Arsenal's bid to return to the UEFA Champions League following their midweek exit at the hands of Bayern Munich continued with a 2-0 success away to Swansea.
January signing Nacho Monreal opened his account for the Gunners with a scuffed effort from outside the box which Swans goalkeeper Michel Vorm will certainly feel he could have done better with.
And the much-maligned Gervinho made it two in the closing stages as he rolled home under Vorm after being played in by Aaron Ramsey.
Stoke halted a run of three successive Premier League defeats but there was still very little for the Britannia Stadium faithful to cheer in their 0-0 draw with West Brom.