The Portuguese former Chelsea and Manchester United boss inherits a side packed with quality players but currently 14th in the Premier League table.
AFP looks at five of the most pressing issues in his in-tray.
Win a trophy
Jose Mourinho's first task will be to stop Tottenham's slide. Last season they rubbed shoulders with Manchester City and Liverpool at the top of the league before falling away.
Spurs, and Mourinho, will be desperate to end the club's trophy drought, which has lasted for more than a decade.
They have not won the English top flight since 1961.
As well as his high profile, Mourinho's knack of picking up silverware will have been a huge plus for Spurs chairman Daniel Levy.
For all of Pochettino's success, he was unable to win a trophy for the club in his spell of more than five years in charge.
Tottenham have struggled defensively this season.
They have kept just one clean sheet in the league and conceded seven in a Champions League game against Bayern Munich.
Mourinho is renowned for his ability to build a side that is defensively rigid and he will have to get to work quickly on drilling his new back line.
Sort out contracts
Pochettino faced a major problem after a summer rebuild failed to materialise and he was left with a clutch of players who had appeared to be on their way out of the club.
Christian Eriksen spoke publicly of his desire to quit Spurs at the end of last season and the Dane, along with Jan Vertonghen and Toby Alderweireld, is in the final year of his contract.
Eriksen, Danny Rose -- also linked with a move away -- and Vertonghen, have performed well below par this season.
Mourinho must find a way to unite the squad quickly and get the best out of his players, some of whom could leave the club as early as January.
Tackle away form
Part of Pochettino's demise was due to poor away form. Spurs have won just three times on the road since January -- all in the Champions League.
That is not good enough for a side of Tottenham's quality.
Convince Harry Kane to stay
While the fate of players such as Eriksen, Vertonghen and Alderweireld may be out of his hands, Mourinho needs to convince Harry Kane that his future remains at Spurs.
The England captain is under contract for plenty of time yet, but he is a superstar of European football and has always said he wants to win things.
Ideally that would be at Spurs, and his chances of that might just have improved, but it would be a surprise if he were not linked with the super clubs this summer, especially if he has a good Euro 2020.
Mourinho needs to do everything he can to make sure Kane, who had a close relationship with Pochettino, still feels content at the club -- and hopefully winning matches will help to convince him.