Anelka's goal earned Megson his first win in six games in charge
Gary Megson claimed his first win in charge of Bolton with the unlikely scalp of Manchester United, thanks to Nicolas Anelka's early strike.
Anelka slotted home Ivan Campo's free-kick after 11 minutes.
And an out-of-sorts United were left frustrated as Jussi Jaaskelainen kept out Owen Hargreaves' free-kick and Carlos Tevez sliced a shot wide.
United boss Sir Alex Ferguson was sent to the stands after the break following a half-time rant at the referee.
Ferguson, whose side now trail Premier League leaders Arsenal by three points, was dismissed by referee Mark Clattenburg for a tunnel outburst at a succession of minor decisions that had gone against his team.
Although Manchester United's trip was less than 20 miles down the road from Old Trafford, the gap between the two sides in the Premier League could not be much bigger.
United experienced their only previous league defeat this season back in August - against Manchester City - whereas that same month marked Bolton's only win in the Premier League - 3-0 against Reading.
Having already notched up four draws and a loss, Megson's side have clearly become harder to beat but few would have expected them to take an early lead.
Megson reaped the rewards of Anelka's return from a recent hamstring injury when the Frenchman took advantage of United defender Gerard Pique's mistake to slot home.
Campo's chipped free-kick set up the goal with Pique mis-timing his leap leaving Anelka unmarked with the ball in front of goal.
While Bolton looked lively and dangerous on the break, the visitors made a lacklustre start - perhaps missing the touch of winger Cristiano Ronaldo, who was rested after playing in two Euro 2008 qualifiers over the past week.
United's chances at the other end were few in the first half with Hargreaves screwing a 20-yard effort wide, and Tevez just failing to get on the end of Rio Ferdinand's long ball.
Ferguson was left fuming by the clashes between Davies and Evra
Their frustrations were deepened by an ongoing battle between Bolton striker Kevin Davies and United defender Patrice Evra - which resulted in an angry Ferguson being sent to the stands after the break.
Davies was lucky to get away with just one booking after two heavy-handed late challenges and a nasty clash of heads with the Frenchman.
But the referee's decision brought Ferguson to the touchline to express his disgust.
However the tactical substitution of Pique for Anderson just before the half hour mark seemed to reinvigorate Ferguson's side and moments later, keeper Jussi Jaaskelainen did well to keep out Owen Hargreaves' dipping free-kick with a flying save.
United kept turning the screw and Carlos Tevez should have done better when he sliced Evra's cross wide from just a yard out 70 minutes in.
Although the visitors continued to pile forward, United could find no equaliser.
And when Hargreaves clipped the roof of the net with an injury-time free-kick, Ferguson had to settle for the sight of his side losing at Bolton for the first time since December 1978.
Meanwhile Megson was able to breath a sigh of relief as defeats for Birmingham, Sunderland, Middlesbrough and Wigan helped Bolton climb from second from bottomin the table to 15th on 11 points.
Bolton boss Gary Megson:
"It's Bolton's second victory not my first. They worked hard for the football club and themselves.
"It was a terrific performance in terms of work-rate, desire and drive.
"It's really good result for us, given the other results around the division. We have an awful lot going for us and I have no qualms in saying we will get out of this position."
Manchester United boss Sir Alex Ferguson on referee Mark Clattenburg:
"I told the referee what I thought - some referees don't like it. They don't like the truth.
"But I just told him how bad he was in the first-half.
"I know Bolton are battling for their lives at the bottom but they were a bit aggressive and we were looking for some protection from the referee."
Bolton: Jaaskelainen, Hunt, Meite, Andrew O'Brien, Gardner, Campo, Nolan (McCann 83), Guthrie (Wilhelmsson 74), Davies (Speed 70), Anelka, Diouf.
Subs Not Used: Al Habsi, Michalik.
Booked: Davies, Nolan, Hunt.
Goals: Anelka 11.
Man Utd: Van der Sar, Brown (O'Shea 88), Pique (Anderson 59), Ferdinand, Evra, Nani, Carrick, Hargreaves, Giggs, Saha, Tevez.
Subs Not Used: Kuszczak, Fletcher, Eagles.
Ref: Mark Clattenburg (Tyne & Wear).