Arsenal kept their top-four hopes alive and ended Manchester United's 25-match unbeaten run in the Premier League with a 2-0 victory at the Emirates on Sunday.
United made eight changes from their Europa League semi-final first leg against Celta Vigo on Thursday, and they fell behind shortly after half-time as Granit Xhaka's long-range shot deflected over David de Gea and into the net.
Danny Welbeck doubled the lead three minutes later and Arsenal comfortably held on to give Arsene Wenger his first competitive win over Jose Mourinho.
The victory also keeps Arsenal in the hunt for a top-four finish, although they still need either Liverpool or Manchester City to drop points.
The Gunners are seven points behind Liverpool with two games in hand, while defeat is United's first in the league since October 23, and leaves them four points outside the top four with three games left to play.
United did have their top-four fate in their own hands after Liverpool's draw with Southampton earlier in the day, but Mourinho, perhaps with one eye on the Europa League return leg with Celta Vigo on Thursday, opted to rotate his starting line-up at the Emirates.
Axel Tuanzebe was handed a first Premier League start while Phil Jones and Chris Smalling returned in defence and Eric Bailly, Paul Pogba and Marcus Rashford dropped to the bench.
The Gunners made two changes from their defeat at Tottenham as Rob Holding started in place of Gabriel and Welbeck replaced Olivier Giroud up front.
Wayne Rooney captained United and he flicked an early cross over the bar before sliding through Anthony Martial, who shot at Petr Cech.
De Gea then made a good save on the stretch at the other end to deny Aaron Ramsey after a through ball from Alexis Sanchez.
Although Arsenal largely looked the more threatening side, they took until the half-hour mark to create further chances.
Welbeck saw a couple of close-range shots blocked before Alex Oxlade-Chamberlain's deflected effort was pushed away by De Gea.
But just as it seemed as though Arsenal were starting to raise the tempo, Holding almost gifted United the opener with a pass across his own goal that was picked up by Rooney, whose shot was saved by Cech.
United continued to frustrate the hosts after half-time, but they were undone in the 54th minute when Xhaka's 30-yard attempt deflected off Ander Herrera's back and looped over De Gea.
Welbeck made it 2-0 three minutes later, heading in off the bar from Oxlade-Chamberlain's cross.
Rooney went closest to a response for United as he saw a free-kick saved and then fired over the bar from the edge of the box, but otherwise it was comfortable for Arsenal as they recorded a much-needed win.
Arsenal: Cech (6), Holding (6), Koscielny (8), Monreal (7), Oxlade-Chamberlain (7), Xhaka (7), Ramsey (8), Gibbs (6), Ozil (6), Sanchez (6), Welbeck (7).
Subs: Giroud (5), Bellerin (5), Coquelin (5).
Manchester United: De Gea (6), Tuanzebe (6), Jones (5), Smalling (5), Darmian (5), Herrera (6), Carrick (6), Mkhitaryan (5), Mata (5), Martial (5), Rooney (5).
Subs: Lingard (5), Rashford (5), McTominay (5).
Man of the match: Aaron Ramsey.