Among those to return to the starting lineup for United are Antonio Valencia and Nemanja Matic, who have missed the opening two games of the season through injury, while Jesse Lingard starts for the first time after a reduced pre-season.
Asked about his decision to change more than half of his side for the visit of Spurs, Mourinho told Sky Sports News: "We didn't play well [at Brighton], we made mistakes, we change the team.
"The match before [against Leicester City] we played well, no mistakes, total control, deserved victory, we didn't change the team. If I don't play Valencia, Matic, Lingard when they are ready, I don't think you'd accept it, you'd ask why I didn't play important players if they were ready.
"[Matic] is always the same, he is a play that gives balance, experience. Andreas [Pereira] was playing really well, but Matic is a different player, I don't mean level of quality but level of experience. I think we need that."