However, leader Chelsea had its first real stumble, failing to score for the first time this season and being held to a 0-0 draw at Sunderland.
United's 3-0 victory over Hull ensured the Red Devils will complete a second successive weekend in the top four for the first time since Alex Ferguson retired as manager after winning the 2013 title.
After a poor season under David Moyes, manager Louis van Gaal is slowly rebuilding confidence while contending with injuries as United pushes for a return to the Champions League.
United's opener came from a surprise source, with defender Chris Smalling scoring his first goal in 11 months, with goal-line technology confirming goalkeeper Allan McGregor failed to keep it out. Van Persie is expected to be finding the net regularly, but hit only his fourth goal of the season — a 66th-minute strike into the roof of the net — after setting up Rooney's fifth just before half time.
"It is the first match that we have dominated the game from the first minute until the last minute and in a way that I like," Van Gaal said.
United cut its deficit to 11 points behind leader Chelsea, which was kept in check by a defensive-minded Sunderland.
"The other team wanted to stop us winning," Chelsea manager Jose Mourinho said. "To defend well and a lot isn't a crime. It's part of the game. It's strategy. My players tried everything."
Arsenal and Liverpool are out of the top four despite both posting 1-0 victories on Saturday. Glen Johnson's late scrambled header enabled 11th-placed Liverpool to overcome Stoke, while Danny Welbeck's goal at West Bromwich Albion sent Arsenal up to sixth.
"Our solidarity got us through when the legs went in the last 10 minutes," Arsenal manager Arsene Wenger said. "Defensively we were maybe a bit more stable today."
West Ham rose to fifth by ending Newcastle's five-game winning run. Aaron Cresswell clinched the 1-0 victory early in the second half before Newcastle midfielder Moussa Sissoko was sent off in the 76th after receiving two quick yellow cards.
Queens Park Rangers climbed off the bottom after Charlie Austin clinched a 3-2 victory over Leicester, which sunk to the foot of the standings. Burnley remains sandwiched between QPR and Leicester, after Danny Ings scored a late penalty to cancel out Joe Cole's goal for Aston Villa in a 1-1 draw.
There was also a 1-1 draw between Swansea and Crystal Swansea. Mile Jedinak, who scored Palace's equalizer from a penalty, paid a pre-match tribute to fellow Australian Phillip Hughes, placing a cricket bat on the field to honour the cricketer who died after being hit by a ball.
On Sunday, there's a meeting between second and third with Southampton hosting champion Manchester City, while Everton is at Tottenham.