Wayne Rooney scored twice in the second half and Cristiano Ronaldo played a part in all four goals to help Manchester United crush Aston Villa 4-0 to charge six points clear in the Premier League on Saturday.
Champions United, who also netted in the first half with a cheeky Ronaldo back-heel and a header from Carlos Tevez, lead second-placed Arsenal by six points with six games remaining.
Arsenal, down to 10 men for an hour, ended a six-year league jinx at Bolton Wanderers as they fought back from two goals down for a 3-2 win.
Chelsea, two points further back, can reclaim second spot by beating Middlesbrough on Sunday when Liverpool and Everton also resume their battle for fourth place in the Merseyside derby.
At Old Trafford, where the second half was played in pouring rain, the league's top scorer Ronaldo took his tally for the season to 26 when he struck in the 17th minute.
A cross was poorly cleared and the loose ball fell to the Portugal striker who, with his back to goal, flicked it with his left heel through defender Martin Laursen's legs and past keeper Scott Carson.
Tevez made it 2-0 just past the half hour when he dived to head home Ronaldo's far-post cross following a fine team move started on the halfway line by the Argentine.
Ronaldo flicked on a Ryan Giggs pass for Rooney to take the ball round Carson for the third in the 53rd minute, his first goal in eight games.
Rooney added the fourth in the 70th minute from another Ronaldo pass, taking his league tally to 10.
Looking ahead to United's Champions League quarter-final first leg at AS Roma on Tuesday, Rooney told Sky Sports television: "It's going to be a massive game for us in Rome. I think we prepared well today".
DIABY OFF
Arsenal manager Arsene Wenger will also look forward with optimism to Wednesday's first leg at home to Liverpool after his side's gutsy fightback at Bolton.
Midfielder Matthew Taylor put Bolton two up in the first half with goals either side of the dismissal of Arsenal's Abou Diaby for a high tackle on Gretar Steinsson.
Captain William Gallas led Arsenal, who had not won at the Reebok Stadium in their previous five league visits and had lost on their last three, back into the match when he turned in Cesc Fabregas's corner in the 63rd minute.
Robin van Persie equalised with a penalty five minutes later after Gary Cahill brought down Alexander Hleb and an own goal by Jlloyd Samuel following Fabregas's 90th-minute shot ended Arsenal's run of five league games without victory.
"It was important to get into a winning way again," said Wenger. "I know the mental strength of this team, they can dig deep."
Derby County were relegated after a 2-2 draw at home to Fulham, Birmingham City's 3-1 win over Manchester City sealing the bottom team's fate.
It is the first time a Premier League team has been relegated in March, Derby breaking the record set by Sunderland in 2003 when they went down on April 12.
Derby have taken 11 points from 32 games and will now hope to exceed 15 points, another Sunderland record from 2006.
Sunderland boosted their bid to avoid another quick return to the second tier with a 2-1 home win over West Ham United.