Rowan Vine grabbed a controversial winner, but Hatters should have scored more against nine-man Chesterfield.
Town made one change to the side that lost 4-3 at Boston after extra time in Tuesday's Carling Cup thriller.
Kevin Foley returned to right-back after his call up to the Republic of Ireland Under-21s squad at the expense of Lee Mansell, meaning Ahmet Brkovic moved back to his more familiar right-wing role.
Keith Keane, also missing in midweek due to Eire Under-19 action, was on the bench.
Hatters started strongly and Steve Robinson fired just wide from 20 yards with 90 seconds on the clock after Paul Underwood's through ball to Vine fell into his path.
Two minutes later, Town almost took the lead when Vine held off three defenders to bundle his way into the right side of the penalty area and his cross-shot bounced away off the far post.
Vine should have done better in the 12th minute when he ran clean through on to Brkovic's pass, but tried to round Carl Muggleton and ran the ball out for a goal-kick.
Luton's dominance continued when Robinson broke free down the right and squared to Howard whose shot was pushed away by Muggleton in the 22nd minute.
Just seconds later, Foley's hanging cross dropped to Howard in the box, but the big striker couldn't convert.
Chesterfield registered their first shot on target in the 25th minute when the lively Jamal Campbell-Ryce ran across the penalty area and centred for Wayne Allison, but the veteran striker's header was held by Marlon Beresford.
Howard then picked up his fourth caution of the season for a clumsy tackle on Shane Nicholson, but the Chesterfield full-back was lucky to escape with just a yellow card of his own after he retaliated and appeared to stamp on the Luton hitman.
Howard was involved in another moment of controversy eight minutes before half-time when he raced on to Kevin Nicholls' through ball and appeared to be caught by Muggleton, but Luton's penalty appeals were ignored by referee Brian Curson.
Two minutes later Hatters went close again when Chris Coyne headed back Robinson's free-kick and Howard laid back to Paul Underwood, whose toe-poke was saved by Muggleton.
Forty five seconds after the restart Curtis Davies forced Muggleton to push his 15-yard shot aside after Coyne's knock-down from Davis' free-kick. Beresford then superbly stopped Mark Allott's 20-yard shot three minutes later as Chesterfield countered.
But the home side took the lead in the 49th minute when Vine chased Coyne's long clearance, bundled over Alan O'Hare and slammed the ball home from 10-yards.
Chesterfield protested angrily over Vine's strong challenge, but the goal stood.
The day got worse for the Spireites when Steve Blatherwick was sent-off for hauling down Vine as he ran clear on goal again in the 75th minute.
Nicholson was given his marching orders for a second yellow card in stoppage time.