He replaces Nuno, who spent just 17 matches in charge.
Tottenham have appointed former Chelsea and Inter Milan boss Antonio Conte as their new manager until summer 2023.
“I am extremely happy to return to coaching, and to do so at a Premier League club that has the ambition to be a protagonist again."
The Premier League club sacked Nuno Espirito Santo after just 17 games, with Spurs eighth in the table.
In a club statement released Tuesday, Tottenham says there is "an option to extend" 52-year-old Conte's deal with them.
The move comes 5,000 days to the day since Tottenham won their last trophy - a 2-1 win over Chelsea in the 2008 league cup final on February 24, 2008.
The Italian returns to London after winning the Premier League in his first season at Chelsea in the 2016-2017 season - and the FA Cup in his second before being sacked in 2018.
He then led Inter Milan to their first Serie A title in 11 years before leaving the club in May by "mutual decision".
Conte was then in talks with Tottenham in the summer about becoming Jose Mourinho's successor. But negotiations were halted before Spurs appointed ex-Wolves boss Nuno at the end of June, with the Portuguese manager lasting just four months.