Jose Mourinho's side had prevented their neighbours winning the title with a stirring comeback last weekend, but an unlikely defeat to the Baggies secured a third Premier League title for their cross-city rivals.
United were second-best all afternoon and Darren Moore's men earned their reward for a spirited display thanks to Jay Rodriguez's close-range header 17 minutes from time.
Romelu Lukaku was twice denied by smart saves from Ben Foster, while Jesse Lingard also came close after his introduction from the bench at half-time.
The hosts threw everything at West Brom in the closing stages, but were unable to find a breakthrough that would have delayed City's title confirmation until at least Wednesday when United take on Bournemouth.
Victory for West Brom moves them up to 24 points, but they remain nine away from safety with just four games remaining.
Not for the first time this season at Old Trafford United started sluggishly and could have been a goal down after 12 minutes.
Ander Herrera had his pocket picked midway through his own half by Rodriguez before the ball was rolled into the path of Jake Livermore. The England midfielder's effort lacked venom, though, and was parried to safety by David de Gea.
Herrera had a penalty appeal waved away after seemingly being tripped by Craig Dawson, while Lukaku's powerful drive from Juan Mata's through ball was kept out by the face of Foster.
United's insipid half was then summed up when Paul Pogba received a yellow card for inexplicably trying to convert a deep cross with his hand.
Lingard replaced Herrera at the interval and the new man almost made an immediate impact with a fierce goal-bound drive that was bravely blocked by Dawson.
Mata sliced wide from just outside the penalty area before the ineffective Pogba was hauled off for Anthony Martial just before the hour in a desperate attempt to inject some spark into United's lifeless attack.
Lukaku must have thought he had broken the deadlock after 65 minutes but former United goalkeeper Foster got down superbly to repel the Belgian's powerful header from Nemanja Matic's cross.
And the importance of that save was brought into sharp focus eight minutes later as Rodriguez stole in unmarked to nod in Matic's wayward header from a corner.
United pushed numbers forward in the closing stages, but Foster never really looked in danger of being tested again as United succumbed to a defeat that was celebrated by the blue half of Manchester with even more vigour than usual.
Key Opta stats:
- West Brom have lost just one of their last five Premier League visits to Old Trafford (W3 D1 L1), with their only loss in this run coming in November 2015 (0-2).
- This was just the second time in Premier League history that Manchester United have lost at Old Trafford to a side starting that day as the bottom of the league club – the other game was a 2-3 defeat to Blackburn Rovers in December 2011.
- Darren Moore has already equalled Alan Pardew’s total Premier League wins (one in 18 games) as WBA manager in just his second game as boss.
- Jay Rodriguez has scored as many goals in his last four Premier League appearances (three) as he did in his previous 26 combined.