On a potentially pivotal day in the title race and relegation battle, West Brom manager Roy Hodgson tasted victory over former employers Liverpool, Newcastle got the better of Wolves, Tottenham were held by Wigan and there was major controversy at Goodison Park.
Manchester United had the opportunity to pile pressure on their rivals as they took to the field at Upton Park in the day's early kick-off, but in the end were indebted to a second-half hat-trick from Rooney as West Ham let slip a 2-0 lead to lose 4-2.
Avram Grant's improving Hammers had knocked the Red Devils out of the Carling Cup earlier this season and looked set to seal another shock victory which would have significantly boosted their survival hopes.
Mark Noble scored both their goals from the penalty spot, the first after a Patrice Evra handball and the second after a Nemaja Vidic foul on Carlton Cole, when the Serbian protested that it had occurred outside the area.
United needed something special in the second half and it was provided by a resurgent Rooney, who reduced their arrears with a curling free-kick on 65 minutes.
The England striker equalised with a high-class second after latching onto Antonio Valencia's pass, before putting United in front with a penalty of his own following a harsh handball decision against Matthew Upson.
Rooney's treble came in a breathtaking 14-minute period, and there was still time for substitute Javier Hernandez to add a fourth for United.
Chelsea were unable to respond to United's victory in the manner they wanted as the Blues' title dreams faded following a 1-1 draw with Stoke.
Jon Walters broke the deadlock for the Potters with a stunning solo effort on eight minutes, skipping away down the left before cutting inside and coolly firing past Petr Cech.
Fernando Torres had started on the bench for Chelsea after failing to score since his £50million January switch, and Carlo Ancelotti's selection was vindicated as Didier Drogba athletically headed in an equaliser from Nicolas Anelka's cross.
But Chelsea could not complete the turnaround despite carving out a number of excellent chances, as Stoke held on to maintain their good record at the Britannia Stadium and leave Carlo Ancelotti's side trailing United by 11 points, albeit with a game in hand.
Hodgson admitted this week that his Liverpool reign was not helped by the presence of Kenny Dalglish behind the scenes at Anfield, but the West Brom manager came out on top in their battle of wits at The Hawthorns following a 2-1 triumph that will go a long way toward retaining the Midlands club's Premier League status.
Dalglish's Reds have been in decent form of late but were frustrated in a goalless first half which also saw defenders Daniel Agger and Glen Johnson withdrawn due to injury.
They did not have to wait much longer to make the breakthrough though, as Martin Skrtel directed a header beyond Scott Carson from Raul Meireles' corner.
Chris Brunt drew the Baggies level just after the hour mark with a penalty after Sotirios Kyrgiakos had clumsily brought down Peter Odemwingie just inside the area.
Another spot-kick then proved decisive, as Brunt hammered home his second effort of the afternoon after Reina tripped Odemwingie.
Wolves' fine recent run came to an end as Newcastle eased their own relegation fears with an emphatic 4-1 success at St James' Park.
Kevin Nolan made a well-timed run from midfield to seize on a Shola Ameobi flick-on and place his shot past Wolves goalkeeper Wayne Hennessey midway through the first half to give Newcastle the lead.
Wolves' frail defence was again exposed on the stroke of half-time when Ameobi rose highest at the back post to powerfully nod home Peter Lovenkrands' left-wing delivery.
Lovenkrands then got in on the act with a third for Newcastle in the 50th minute, before Sylvan Ebanks-Blake pulled one back for the visitors.
Jonas Gutierrez completed the rout for the Magpies late on to further dent Wolves' goal difference.
Birmingham picked up a vital 2-1 victory over Bolton to move out of the drop zone and gain revenge for their FA Cup exit at the hands of the Trotters last month.
Birmingham have slipped into deeper Premier League trouble since winning the Carling Cup at the end of February but in Kevin Phillips they have a player with experience of tough situations, and the veteran striker gave them an ideal start with a fourth-minute strike that proved too powerful for Jussi Jaaskelainen to keep out.
Craig Gardner made it 2-0 with a fine effort off the post in the 59th minute, only for Johan Elmander to respond for Bolton courtesy of a volley 11 minutes later.
Bolton battled hard in an effort to rescue a point but Birmingham held firm to take the spoils.
Everton and Aston Villa both had reason to feel aggrieved at refereeing decisions following a dramatic 2-2 draw at Goodison Park which is sure to reopen the debate into goal-line technology.
Darren Bent's slick double looked set to seal victory for Villa and put an end to talk of a revolt against manager Gerard Houllier, but Leighton Baines salvaged a point for Everton after match official Mike Jones controversially adjudged that Jean Makoun had fouled Phil Jagielka.
Diniyar Bilyaletdinov did well to release Leon Osman for the opening goal on 38 minutes, although Brad Friedel could perhaps have got a firmer hand on the midfielder's shot.
Stewart Downing and Bent, two of the players to impress for England last week, combined for Villa's leveller at the start of the second period as the former Sunderland striker converted stylishly from the winger's cross.
But the real turning point came in the 68th minute when the referee waved play on after a Jermaine Beckford strike crashed down off the underside of the crossbar, with replays suggesting it may have just crossed the line, and Bent scored at the other end moments later with another composed finish.
Baines' late equaliser eased some of Everton's pain, but Villa may also feel hard done by as they remain precariously placed just above the drop zone.
Tottenham could only warm up for Tuesday's trip to Real Madrid in the UEFA Champions League with a goalless stalemate against bottom club Wigan.
Having also been held to a 0-0 draw by London rivals West Ham before the international break, Spurs were again missing a creative spark as their top-four chances suffered a setback.
The Latics, meanwhile, inch a step closer to survival but remain at the foot of the table, with Wolves and West Ham also in the bottom three.