The Hatters finished 6th in the table, which set them up to face Carlos Corberan’s side, who finished 3rd.
The Terriers won the latest league meeting between the two sides, coming out 2-0 victors at the John Smith Stadium.
But the clash at Kenilworth Road ended 0-0, with both sides sharing the spoils in October.
A good first leg result will be essential in putting one foot in the Wembley final, as both sides look to chase promotion to the Premier League.
Latest team news
Luton’s injury concerns have decreased going into this week’s clash, but there are still numerous players expected to be unavailable for selection.
The likes of Luke Berry, Pelly-Ruddock Mpanzu, Elijah Adebayo and Fred Onyedinma are all set to miss out on the first leg action.
Quiz: Which club did Luton Town sign these 24 players from in the 2000s?
Huddersfield have had injury concerns of their own in recent weeks, with the likes of Sorba Thomas and Matty Pearson unavailable for selection in the final day of the regular season.
Duane Holmes and Lewis O’Brien have also had injury concerns in recent weeks, but Corberan is confident that both will be passed fit to feature at Kenilworth Road.
Huddersfield Town to win 1-0.
Is there a live stream? Is it on TV?
Coverage of the game is being broadcast on Sky Sports Main Event, with a start time of 7pm.
This is also available via Now TV with a Sports Pass.
What time is kick-off?
The game kicks off at 7.45pm.