Leandro Trossard, Danny Welbeck and Neal Maupay were on target for Brighton as for once this season Graham Potter's men turned their dominance into goals.
Chelsea made it four wins from four matches in Group L by edging out a spirited BATE Borisov 1-0 in Belarus.
England were denied a point when referee Danny Makkelie awarded a foul in favour of Spanish goalkeeper David de Gea for minimal contact with Danny Welbeck.
Arsenal registered a 5-1 aggregate win over AC Milan in the Europa League last 16 to reach their first European quarter-final since 2010.
Danny Welbeck, 25, has made 35 appearances for England and scored 14 international goals
Danny Welbeck and Alex Iwobi netted a goal each as Arsenal F.C. defeated Everton F.C. 2-0.
Arsenal's loss to Watford on Sunday was their first defeat in the FA Cup since a 1-0 fifth-round defeat by Blackburn Rovers in February 2013.
Marcus Rashford marked his Premier League debut for Manchester United by scoring in the 29th and 32nd minutes, three days after a double in the Europa League against FC Midtjylland.
Fielding a weakened team, Arsenal created a slew of chances but were denied by a mixture of poor finishing and good goalkeeping from Eldin Jakupovic.
Danny Welbeck's goal, after fellow substitute Theo Walcott had cancelled out Jamie Vardy's first-half penalty, saw Arsene Wenger's men complete a league double over Leicester following their 5-2 win in September.