Adam Le Fondre struck twice in the opening 45 minutes to give Bolton a first Sky Bet Championship double of the season and push Millwall closer to the drop.
But new Lions boss Neil Harris was left to rue a batch of missed second-half opportunities that cost the Londoners a share of the spoils.
As a result Millwall’s sixth defeat in their last seven games pushed them closer to relegation.
In contrast, Wanderers gained one of three victories that manager Neil Lennon believes will banish any outside chance of them dropping down into the third tier.
On-loan Cardiff striker Le Fondre now has five goals since returning to the north west as Wanderers bounced back from their midweek defeat at Blackburn.
Le Fondre was still in south Wales when a Darren Pratley goal earned Bolton victory at Millwall last December, but this brace extended Wanderers unbeaten home record against their visitors, dating back to 1973.
The one-time Stockport and Rochdale favourite broke the deadlock after 12 minutes with a sweet finish from Tim Ream’s pass.
Just before the break he doubled his tally with an equally impressive finish. This time Eidur Gudjohnsen claimed the assist, with Lions skipper Alan Dunne appealing in vain for offside.
Le Fondre took the ball into the area before dispatching a curling righted-foot shot beyond David Forde’s despairing dive.
In contrast, Millwall offered little in the first 45 minutes to trouble another of Lennon’s nine-strong loan brigade, goalkeeper Ben Amos.
Harris made five changes to the team that started the previous 4-1 defeat by Norwich, with Shaun Cummings restored to the side after a thigh problem, but with no place for Wanderers’ January transfer target Diego Fabbrini.
Lennon brought back Gudjohnsen and midfielder Barry Bannan from the team beaten 1-0 by Jordan Rhodes late goal at Ewood Park. And the Trotters chief had to make an unscheduled change when Manchester United loanee Saidy Janko suffered injury in the warm-up.
Youngster Tom Walker stepped up from the bench for a full debut.
And Bolton made an immediate change for the start of the second half. Neil Danns, booked and also spoken to for first-half fouls on Shaun Williams, was replaced by Giles Coke to avoid a repeat of his FA Cup fourth-round replay sending-off against Liverpool.
Coke tried his luck with a long-range shot from ex-Millwall winger Liam Feeney’s cross. And 19-year-old Walker also was not too far wide as Wanderers tried to kill off the game with a third goal.
Having failed to do so they were forced to absorb constant Millwall pressure that should have resulted in a lifeline. Only a vital Ream challenge on Gary Taylor-Fletcher prevented Millwall pulling a goal back.
And the visitors went even closer after 59 minutes.
Coke was dispossessed 40 yards from the Millwall goal and Ed Upson’s measured pass sent Lee Gregory racing through on goal, only for Amos to block the striker’s tame shot.
Amos, out of contract at Old Trafford at the end of the season, then kept out an even better chance for Aiden O’Brien after Lee Gregory’s defence-splitting pass
Despite their best endeavours, the Lions could not find a breakthrough and Bolton finished on top, with Forde denying Walker a debut goal from a sweetly struck free-kick.