Aston Villa and West Ham were also beaten away at Championship opposition, while West Brom and Reading could only manage draws against lower league sides.
But it was the champions of Europe who will attract the headlines as they blew an early lead to lose 3-1 at the Amex Stadium.
Frank Lampard gave Roberto Di Matteo’s men the lead before goals from Vicente, Ashley Barnes and Andrew Crofts saw the Seagulls to a memorable win.
Villa were also on the receiving end of a 3-1 defeat at the hands of Nottingham Forest.
Lewis McGugan hit a brace and Marcus Tudgay scored the other with Barry Bannan’s free-kick the only positive for Paul Lambert’s side.
Ipswich also inflicted a 3-1 loss on Premier League opposition as they beat Sam Allardyce’s Hammers at Portman Road.
Michael Chopra scored a penalty before Luke Chambers and Jason Scotland added further goals with only a Matty Taylor effort to cheer the away side.
Albion and Reading held
West Brom were spared a defeat thanks to Peter Odemwingie’s late equaliser cancelling out a fine goal from Sheffield Wednesday new boy Nejc Pecnik.
Reading were also forced to settle for a draw as they shared two goals apiece at Bournemouth.
Wesley Thomas and Miles Addison netted for the Cherries with Adrian Mariappa and a Hal Robson-Kanu penalty providing the goals for the visitors.
The only Premier League winners were newly-promoted Southampton as they beat Wolves 2-0 in front of sparse crowd at St Mary’s.
A goal in each half for Billy Sharp and Jason Puncheon were enough to see off a poor Wolves side.
In France, Mladen Petric continued his fine goalscoring form in pre-season as bagged again in Fulham’s 4-0 win over Nice.
Petric scored a delightful scissor kick to put the Cottagers ahead and has now scored in every pre-season game since arriving at the club earlier this summer.
Alex Kacaniklic put the west London outfit two goals ahead just before the interval.
Mahamadou Diarra notched a the third goal before the exciting teenager Mesca rounded off the scoring.
Later in the night, Manchester City beat Wolfsburg 2-0 at the Volkswagen Arena with goals from Sergio Aguero and Yaya Toure.