Bruno Fernandes had the game’s first opportunity when his long-range effort was parried to safety by Matz Sels, but it was Forest who broke the deadlock from United’s resulting corner in a blistering solo counterattack from Anthony Elanga.
The former Red Devils winger picked up the loose ball from Ryan Yates’ headed clearance and made a superb marauding run down the pitch, before dispatching a clinical left-footed finish past Andre Onana.
It was the 23rd match in all competitions which United had conceded the opening goal, with only Leicester (25) doing so on more occasions among Premier League sides.
Ruben Amorim’s men responded well though as Casemiro headed wide from a Fernandes corner. Fernandes was causing problems for the Forest defence with his corner deliveries and teed up Portuguese compatriot Diogo Dalot, whose header cannoned off the bar.
Aside from Elanga’s stunning opener, the Tricky Trees offered little more going forward, and were dealt a blow when Ola Aina was forced off injured before half-time.
The game continued at a frenetic pace after the break, as Morgan Gibbs-White rifled an attempt over the bar after Alejandro Garnacho lost possession in his own half.
The Argentine took matters into his own hands at the other end of the pitch, as his speculative effort drifted narrowly wide before seeing an effort in a promising position blocked by Yates.
United were playing some fine football without finding the necessary cutting edge to break down a seemingly impenetrable Forest defence, with Sels left largely untroubled between the sticks.
The Belgian made a routine stop to collect Patrick Dorgu’s header, with Fernandes the architect of another opening from the visitors.
Mason Mount was introduced for his first appearance since mid-December, and almost capped off his return with a goal when his curling effort sailed inches wide of the post.
Fellow substitute Harry Maguire headed wide from Dorgu's cross before seeing a late effort cleared off the line by Murillo as Forest clung on to claim a gritty victory which epitomised what has been an outstanding campaign that extended their unbeaten home league run to nine games to strengthen their grip on third place.
Meanwhile, United succumbed to consecutive away league defeats to Forest for the first time since 1990 and remain down in 13th.
Flashscore Man of the Match: Anthony Elanga (Nottingham Forest)