Dimitar Berbatov's late winning game cruelly denied Wanderers what would have been deserved point against title-chasing Manchester United.
The Bulgarian - as he did at the Reebok two season ago - bagged a decisive late strike just three minutes from time to cement the Reds' place at the summit of the Barclays Premier League.
It had looked like Bolton would be returning to the Reebok with a creditable draw to their name had it not been for the half-time substitute's follow-up effort late on.
A point was the least Bolton deserved after they too came close on several occasions to notching a goal or two, most notably through Johan Elmander's free-kick and Matt Taylor's header in the second half.
Aside from the result, Wanderers also suffered the blow of seeing Stuart Holden carried from the field on a stretcher 15 minutes from the end following a challenge with Jonny Evans, which saw the defender issued with a straight red card as a result.
Wanderers continued where they left off at St Andrew's the previous weekend as they enjoyed an extremely positive start to proceedings at Old Trafford.
Indeed, the Whites could have been one goal to the good inside the first five minutes had Fabrice Muamba managed to get a firmer control on the ball just eight yards out.
Gretar Steinsson and Johan Elmander combined down the inside right channel and when the Swede played the ball across, Muamba stumbled and was unable to make the most of a clear sight on goal.
Wanderers shifted the ball around nicely on the lush Old Trafford turf and there were further opportunities for Stuart Holden, who curled over the bar with his left foot from just outside the area, and Martin Petrov, whose 25-yard free-kick was well held by Edwin van der Sar.
Likewise - and as expected for a team that has won 13 home matches this season - Manchester United looked threatening in attack as the strike duo of Wayne Rooney and Javier Hernandez also forged out decent openings.
Rooney flashed wide with a vicious half-volley from distance and Hernandez felt his team should have been awarded a penalty for a handball when the Mexican's shot struck Gary Cahill inside the six-yard box.
The pair had played an influential role in Manchester United's midweek Champions League win over Marseille and Hernandez's movement and Rooney's vision were particular elements of the home side's play that Wanderers had to be wary of.
This was notable on 35 minutes when Rooney found space inside the box and, from a position on the byline, cut the ball back for the number 14, who clipped just wide of the near post having nipped in front of his marker.
Rooney blazed just over the bar shortly before the interval but they were the only real chances for United inside the first-half as Wanderers gave as good as they got, both in attack and defence.
Bolton too had further chances towards the end of the opening 45 minutes. Patrice Evra threw his body in front of an Elmander volley following a sweeping move down the left, while Muamba's second effort of the a game on 43 minutes - a shot to nothing from 30 yards - was well wide of the mark.
To credit Wanderers' performance in the first-half, Sir Alex Ferguson rang the changes at the break as Dimitar Berbatov and Fabio were brought on for Javier Hernandez and Wes Brown respectively.
It was more of the same at the start of the second period as Wanderers continued to play in a disciplined fashion, restricting the hosts to just two long-range efforts from Nani, one of which brought a low save from Jussi Jaaskelainen and another which flew harmlessly wide of the target.
On the hour mark Owen Coyle decided it was time to unleash the FA Cup quarter-final match-winner Chung-Yong Lee, who replaced Daniel Sturridge.
Elmander was shifted up top as a result, and his commitment and desire created a chance for Kevin Davies on 65 minutes.
The Swede's persistence inside the box culminated in the ball being cut back to the Bolton captain, but his first-time effort was charged down by Evans inside a packed penalty box.
As time ticked by the anxiety levels increased around the full-to-capacity Old Trafford. United pressed and probed but Bolton's rearguard - marshalled excellently by Wheater and Cahill - stood strong.
This was evident none more so than when Berbatov found himself with a clear run on goal, only for Cahill to make up the ground and produce a certain goal-saving tackle on the edge of his own area.
The game took a cruel twist 15 minutes from time when Jonny Evans was shown a straight red card for a mistimed challenge on Stuart Holden five yards outside the Manchester United penalty box.
It became apparent seconds after the tackle that Holden had received a serious looking injury as the Bolton players in unison signalled for medics to enter the field and treat the midfielder. And after several minutes worth of attention, Holden was stretchered from the field with Matt Taylor introduced as his replacement.
From the resulting set-piece, Elmander struck a low, fizzing free-kick which missed the far post by the narrowest of margins as Bolton looked to be the team in the ascendancy with Manchester United operating with ten men.
And arguably the clearest of all Wanderers' opportunities fell to Taylor in the next attack when he guided his free header from Steinsson's cross straight at Van der Sar. If it had been directed anywhere else then it would have surely resulted in a goal.
But, in the harshest possible way, it was the home side that went on to get the all-important winning goal in the 87th minute.
After Nani hit an effort from 20 yards, Jaaskelainen parried low to his right and Berbatov converted the rebound from close-range, with the ball just tricking over the goal-line.
The United fans went wild in the knowledge that their team had got out of jail after being given a real run for their money by a Bolton team that once again showed they can compete with the Premier League's elite clubs.
Manchester United: Van der Sar, Evans, Brown (Fabio 46), Smalling, Evra, Giggs, Carrick, Nani, Valencia, Rooney, Hernandez (Berbatov 46) (Subs not used: Kuszczak, Owen, Park, Gibson, Gill)
Bolton: Jaaskelainen, Steinsson, Cahill, Wheater, Robinson, Petrov, Muamba (Klasnic 90), Holden (Taylor 76), Elmander, Sturridge (Chung-Yong Lee 60), Kevin Davies (Subs not used: Bogdan, Taylor, Rodrigo, Blake, Alonso)