Clarke, who can play in either midfield or defence, will be sidelined for up to six weeks after having an exploratory operation on the same knee that kept him sidelined for three months earlier this season.
Clarke, brother of central defender Nathan, missed the weekend's FA Cup win at Port Vale, as did winger Anthony Pilkington, who was rested due to a thigh strain.
Pilkington is expected to return against Tranmere, but Terriers manager Lee Clark will still be without striker Robbie Simpson and Danny Drinkwater, on loan from Manchester United, as both players are struggling with thigh injuries.
Clark has no other new injury or suspension problems as Town look to bounce back from the 2-1 defeat at Swindon in their last league outing.
