Juan Mata's early red card was the catalyst for Manchester United's downfall as Salomon Rondon saw West Brom halt a run of four successive wins for Louis van Gaal's men.
Talk of a top-four challenge followed the recent upturn in fortunes at Old Trafford, but Albion ensured a key week would start with a loss for the visitors.
Mata's foolish sending-off midway through the first half gave Tony Pulis' men an advantage they capitalised on, with Rondon's fine finish earning a 1-0 victory that almost certainly secures his side's survival.
The Venezuela striker's fourth goal in six Premier League matches condemned United to a first league defeat at The Hawthorns since March 1984 and saw them fall behind in the race for the Champions League.
West Brom were perhaps unfortunate not to take the lead in a first half which saw Mata pick up the first red card of his club career - and United's first sending-off of the season - after collecting two bookings in less than three minutes.
Van Gaal's men showed signs of recovery as they returned from half-time brightly, only for Rondon to lash home and end Albion's run of 11 winless league fixtures at home to the Reds.
Defeat leaves United three points off rivals Manchester City - who also boast a game in hand - and seemed a distinct possibility after a lacklustre opening period.
Anthony Martial's tame effort after two minutes was all Van Gaal's side could muster, whereas the hosts proved a threat from the outset.
Rondon's directness made him a nuisance but it was his vision that almost undid United, with his clipped ball to Craig Dawson headed wide in the ninth minute.
Saido Berahino's scuffed attempt from a clever Craig Gardner header was blocked by the returning Chris Smalling as the home side continued to press, with the natives unhappy to see Daley Blind's high foot on Berahino adjudged to have taken place outside the box.
The noise inside the Hawthorns rose several notches with that decision and - shortly after Gareth McAuley headed inches wide, unaware the offside flag was raised - it went up further.
Less than three minutes after being booked for encroaching on a quickly-taken free-kick, Mata's wild swing at former team-mate Darren Fletcher led to a second yellow.
It naturally led pressure to mount on United's backline, but the closest Albion came before half-time was an audacious half-volley from the unlikely source of Dawson.
Van Gaal's men attempted to capitalise on those missed opportunities as they returned from the break brightly.
Marcus Rashford was largely anonymous but saw a snapshot deflect wide after exceptional work down the left by Martial.
Jesse Lingard was the next to threaten, cutting back and curling a strike just over from the edge of the box.
Ander Herrera hit a free-kick into the wall as United continued to threaten a West Brom defence destabilised by McAuley limping off, only for replacement Sebastien Pocognoli to create the opener.
After referee Mike Dean waved play on, the ball was played out wide for the Belgian full-back to fizz in a cross that Rondon controlled well and fired home sweetly.
It was a 66th-minute lead that United rarely threatened to cancel out, with the introduction of Memphis Depay in place of 18-year-old Rashford failing to jump-start the visitors.
Most of the play was in their half but, like the visitors, Albion were unable to create any clear-cut chances - not that it mattered in the end.
TWEET OF THE MATCH
"Not a red for me Every foul seems a bookable offence these days." - Former United striker Andrew Cole (@vancole9) doubts Juan Mata deserved an early bath.
Ben Foster: 6 (out of 10)
Craig Dawson: 7
Gareth McAuley: 7
Jonas Olsson: 6
James Chester: 6
Stephane Sessegnon: 6
Claudio Yacob: 6
Darren Fletcher: 7
Craig Gardner: 6
Salomon Rondon: 8
Saido Berahino: 6
Sebastien Pocognoli: 6
James McClean: 6
David De Gea: 6
Matteo Darmian: 6
Chris Smalling: 7
Daley Blind: 6
Marcos Rojo: 6
Ander Herrera: 6
Michael Carrick: 6
Jesse Lingard: 6
Juan Mata: 4
Anthony Martial: 6
Marcus Rashford: 6
Morgan Schneiderlin: 6
Memphis Depay: 6
Timothy Fosu-Mensah: 6
Salomon Rondon has taken his time, understandably, after his summer move from Zenit St Petersburg but the striker is starting to blossom. The 26-year-old's crisp second-half finish capped a fine all-round display which means his goals have banked Albion 14 points this season. Chris Smalling, back after a three-game injury lay-off, was rarely given a rest as the physical Rondon hassled him all game.
MOMENT OF THE MATCH:
Rondon is growing into the Barclays Premier League with every game and he was the match-winner here. The forward netted his eighth goal of the season - and fourth in his last six games - when he drilled past David de Gea after 66 minutes. With Saido Berahino likely to leave in the summer Rondon is fast proving he can be the Baggies' main man next season.
MOAN OF THE MATCH:
What was Juan Mata thinking? He had already been booked for petulantly blocking a West Brom free-kick before swiping wildly at Darren Fletcher. He earned two bookings in just 158 seconds - the first club red card of his career - as he landed his team-mates in trouble. United had to play 64 minutes with 10 men and never recovered from the midfielder's moment of madness.
VIEW FROM THE DUGOUT:
Louis van Gaal would have been fuming with Mata following his first-half red, forcing him into a tactical switch and move Marcus Rashford to the right with Anthony Martial central. It was another defeat which will to add pressure on the Dutchman and seriously damage their hopes of a Champions League place. Tony Pulis looks certain to guide Albion to safety and they are just a point away from his pre-season target of 40 points.
WHO'S UP NEXT
Arsenal v West Brom (March 12, Premier League)
Liverpool v Manchester United (March 10, Europa League)