FA Cup finalists United were without Romelu Lukaku and Alexis Sanchez due to injury and their attack looked blunt without the duo, with Brighton the better side throughout at the Amex Stadium on Friday.
David de Gea, crowned United's player of the year for the fourth time this week, eclipsing Cristiano Ronaldo's club record, made a string of saves to keep his side level during the first half.
But Gross nodded in a Jose Izquierdo cross after the break to score his seventh top-flight goal of the season, Marcos Rojo unable to clear the effort before it crossed the line, to guarantee Brighton will stay in the Premier League.
Chris Hughton's men had been beaten twice by United this season without scoring, but ending a six-game winless run in the Premier League moves them up to 11th.
Jose Mourinho, meanwhile, will be concerned by his side's lack of incision and quality in the final third, with a Wembley clash against former club Chelsea just two weeks away and second place not yet certain.
Marouane Fellaini scored a late winner against Arsenal on Sunday and the midfielder tapped in Marcus Rashford's free-kick in the third minute, but the offside flag was raised.
Brighton had the first effort of note in the 13th minute but Gross' strike did not seriously test De Gea, the goalkeeper then called into more strenuous action to push away a terrific volley from the recalled Glenn Murray.
De Gea was having a busy first half, the goalkeeper tipping over Izquierdo's drive and Shane Duffy proving wasteful with a header from the resulting right-wing corner.
Gross was denied by De Gea at his near post in the 34th minute, the half ending with a sloppy United failing to record a shot on target.
1 - Man Utd have managed just one touch in Brighton's penalty area so far, their joint-fewest number of touches in the opposition box in the first half of a Premier League match this season alongside Man City in April and Chelsea in November. Lacklustre. #BRIMUN pic.twitter.com/BMCFmrpYcw— OptaJoe (@OptaJoe) May 4, 2018
Mat Ryan made a smart stop low to his right to keep out Paul Pogba's shot as United improved after the restart, but they deservedly fell behind in the 57th minute.
Izquierdo did brilliantly down the left and stood up a cross that was met by Gross, a desperate attempt from Rojo to clear the header on the line narrowly failing according to the goal-line technology.
Brighton almost doubled their lead when Izquierdo aimed just wide after United failed to clear a corner, before Juan Mata whipped a free-kick over the crossbar to prompt Mourinho into sending for substitutes Luke Shaw and Jesse Lingard.
Ryan beat away a Rashford drive and the Australia goalkeeper gathered Lingard's long-range strike as United cranked up the pressure, the ineffective Anthony Martial lashing an ambitious volley over.
Key Opta stats:
- Brighton registered only their second win in 19 matches against Manchester United in all competitions, with this their first since a 1-0 victory in the top flight in November 1982.
- United have lost away from home against three newly promoted sides in a league season for the first time in their history, also losing at Huddersfield (2-1 in October) and Newcastle (1-0 in February).
- Jose Mourinho has lost six of his last 10 away Premier League matches in the month of May (W1 D3).
- Pascal Gross has been directly involved in 45 per cent of Brighton's 33 Premier League goals this season (15 - 7 goals, 8 assists).