Spurs sacked Mourinho on Monday six days before the EFL Cup final against Manchester City, with their Champions League qualification hopes hanging by a thread.
Mason took first-team training after that move and will now lead the team for the remainder of the 2020-21 campaign.
The first game for Mason will see seventh-placed Tottenham host Southampton in the Premier League on Wednesday.
Mason will be assisted by Chris Powell and Nigel Gibbs, with Ledley King continuing as a first-team assistant and Michel Vorm as his goalkeeping coach.
Mason, 29, was a Spurs player for eight years after coming through the club's youth system.