Defenders Danny Rose (knee), Jan Vertonghen (ankle) and Toby Alderweireld (hamstring) and forward Erik Lamela (hip) are also out.
Wycombe, fifth in League Two, are without midfielder Matt Bloomfield and forward Dayle Southwell.
Defender Michael Harriman is back in contention, having not played since Boxing Day with a groin injury.
Tottenham face Sunderland in the Premier League on Tuesday and boss Mauricio Pochettino said: "Toby, Danny and Kane are out. We don't want to take any risks but they'll hopefully be available for Tuesday.
"I think Saturday is not a moment to take a risk and Harry was training in Barcelona [during a mid-season training camp] next to the group. But we hope that for Tuesday it is not a problem and he will be available."
Wycombe manager Gareth Ainsworth said: "There's no pressure on us. It'll be a brilliant day for Wycombe Wanderers.
"We want to give a good account of ourselves so we'll give our best and see what happens. We know we can cause them problems. If it takes Tottenham Hotspur to end our unbeaten run then that says something, but I'm hoping we can keep this run going.
"There are fairytales and upsets in this competition. If Spurs aren't at their best then we have a chance. We believe in ourselves."
Tottenham will be without top scorer Harry Kane (groin) for Saturday's FA Cup fourth round tie with Wycombe.