With the sides above them all playing each other in a mouth-watering Sunday programme, United could have closed to within three points of fourth-placed Manchester City but the gloom that has enveloped them most of the season returned as their hopes of Champions League qualification receded.
Anthony Martial's dinked finish shortly before halftime cancelled out Wahbi Khazri's third-minute opener for Sunderland but United fizzled out after the break and Spaniard De Gea could only help Lamine Kone's late header into his own goal.
While United's limp defeat put the spotlight back on under-pressure manager Louis van Gaal, Sunderland's first home league win over United since 1997 raised spirits after a week which saw them sack midfielder Adam Johnson after he pleaded guilty to sexual activity with a 15-year-old girl.
Sunderland remain second from bottom but with the Newcastle United, Swansea City and Bournemouth losing and Norwich City surrendering a two-goal lead against West Ham United, their hopes of avoiding relegation rose.
"This is more than an added bonus for us; this is a massive, massive three points," Sam Allardyce, whose Sunderland side are now only one point away from the safety zone, said.
Newcastle were thumped 5-1 at Chelsea in the late kickoff as the champions produced their best performance of a poor league season to extend their unbeaten run in all competitions to 12 since Guus Hiddink replaced sacked Jose Mourinho.
Pedro scored twice for Chelsea, while Diego Costa, Willian and Bertrand Traore also punished a wide-open Newcastle defence to leave the north east club back in the bottom three on goal difference below Norwich who drew 2-2 with West Ham United.
Norwich, on a run of five consecutive defeats, led 2-0 with second-half goals from Robbie Brady and Wes Hoolahan but their leaky rearguard buckled again and Dimitri Payet and Mark Noble earned West Ham a point.
West Ham could have moved above Manchester United into fifth spot with a win but dropped to seventh, below Southampton after they beat Swansea 1-0 in south Wales.
United have 41 points and look destined for a battle for a Europa League place with Southampton and West Ham who have 40.
"It will be difficult to qualify for the Champions League and the top four now, we know that," United skipper Wayne Rooney told the club's website.
"So it's a sad day in terms of losing three points and we have to somehow move on."
West Bromwich Albion eased their relegation fears, winning 1-0 at mid-table Everton, but Bournemouth's 3-1 home defeat by Stoke City left the south coast club in 15th place and four points above third-from-bottom Newcastle United.
Emmanuel Adebayor scored his first goal since joining Crystal Palace but could not prevent a sixth defeat in seven matches for Alan Pardew's side who lost 2-1 at home to Watford.
Attention turns to the title race on Sunday when leaders Leicester City try and consolidate their five-point advantage at third-placed Arsenal before fourth-placed Manchester City host second-placed Tottenham Hotspur.
(Reporting by Martyn Herman, editing by Pritha Sarkar)
