Nicolas Anelka's eighth goal of the campaign earned Wanderers their first win over the Red Devils since September 11, 2002.
It condemned the Premier League champions to their first defeat since another derby disaster against Manchester City on August 19.
And Ferguson spent the second half of the match banished to the main stand by referee Mark Clattenburg.
The veteran Scot was sent-off for an incident in the tunnel at half-time and United's lacklustre display didn't improve his temper.
Woeful in the opening 45 minutes, the champions posed more problems in the second half.
However, a staggering miss by Carlos Tevez and an Owen Hargreaves free-kick brilliantly turned aside by Jussi Jaaskelainen was the best they could muster.
Bolton had to weather the storm in the second period, but they did it manfully to record only their second league clean sheet of the campaign.
Megson was vilified by large sections of the Bolton supporters when appointed as successor to Sammy Lee.
However, he's quickly winning them over and steering the club away from the relegation zone.
Bolton have lost only once since his arrival and this display was certainly reminiscent of the 'dogs of war' under Sam Allardyce.
United certainly missed Wayne Rooney and Cristiano Ronaldo who helped destroy the Trotters last season
Indeed, both sides made changes from their last Premier League outings - the absence of Nemanja Vidic a big loss to United as it transpired.
Ronaldo was rested after his exploits with Portugal, but United thought they had enough strength in depth to record a sixth successive victory over the Trotters.
However, Megson's arrival has added steel and resilience to Wanderers - personified by the example of Kevin Davies.
Without Vidic, United had no one to withstand the physical presence of the ex-Blackburn striker.
Davies had a running battle with United players in the opening 45 minutes and particularly with full-back Patrice Evra.
Davies was booked and given a final warning by referee Clattenburg, while Evra was fortunate to escape similar punishment as their skirmishes escalated.
Without Vidic, United looked fragile at Wanderers' set pieces from which Anelka's goal came.
Ivan Campo chipped the ball forward, Gerard Pique rashly challenged and the ball dropped to Anelka who swivelled to give Edwin Van der Sar no chance.
With United stunned by the early set-back, Bolton were good value for their advantage, although Van der Sar had little else to keep him occupied.
But that mattered little to Wanderers who now truly believe the only way is up.