Martin Cranie’s own goal and Connor Mahoney’s long-range strike in the second period was enough to give the Lions three points at The Den as Town fell to a second defeat in a row.
Manager Nathan Jones made two changes following defeat against Stoke City on Saturday, with Kazenga LuaLua and Jordan Clark both brought in to start.
Striker James Collins remained out of contention after testing positive for Covid-19 but could be back for the home match against Nottingham Forest next week.
Millwall had more efforts on goal during the first 45 minutes and went extremely close to taking the lead through Smith midway through the half.
The striker rose highest in the box, but his header hit the post and Jed Wallace was denied a goal from the rebound after Simon Sluga got down well to save.
He later prevailed in added time at the end of the first half, providing the assist for Millwall’s opener after heading Connor Mahoney’s corner across goal, which deflected off the unfortunate Martin Cranie into the back of the net.
Town looked positive coming out for the second period but were thankful they didn’t fall two goals behind after Jed Wallace spurned a great chance in front of goal, as he fired wide after a neat one-two with Mason Bennett.
Danny Hylton went down in the penalty area under challenge from Jake Cooper and referee Tony Harrington quickly waved away claims for a penalty, although TV replays suggest the striker may have had a case.
Joe Morrell took to the pitch on the hour mark and almost made an instant impact with a long-range effort, but his attempt was just wide of Bartosz Bialkowski’s goal.
LuaLua followed suit and tried from distance but once more, his shot also went wide of the mark.
Millwall made the Hatters pay with a second goal in the 79th minute through Mahoney. He picked the ball up on the left-hand-side and fired low, in off the post past the helpless Sluga.
The Hatters were denied a late route back into the game after Bialkowski pulled off a remarkable save to deny Cranie’s goal-bound header.
Defeat at the hands of Millwall leaves Town in 10th place as attention now turns to Saturday’s away match against Sheffield Wednesday.
Town: Sluga, Cranie, Pearson (Moncur 87), Bradley (C), Norrington-Davies; Rea, Berry (Morrell 60), Mpanzu; Clark, LuaLua, Hylton (Lee 69).
Subs not used: Shea, Tunnicliffe, Cornick, Lockyer.
Yellows: Cranie
Millwall: Bialkowski, Romeo, Hutchinson, Cooper, Wallace; Wallace, Leonard, Woods, Mahoney (Thompson 86); Bennett (Zohore 80), Smith (Malone 64).
Subs not used: Fielding, Williams, Pearce, Bradshaw.
Goals: Cranie (45+4 og), Mahoney (79)
Yellows: Leonard, Woods
Referee: Tony Harrington