Spurs moved quickly to hire the Italian, who has signed a contract until the "summer of 2023" after on Monday firing ex-Wolves boss Nuno, who was in charge for just 17 games.
Conte, who has also coached Juventus and Italy, won the Premier League with Chelsea in 2016/17 and the FA Cup the following year before he was sacked by the Stamford Bridge club.
The 52-year-old had been out of work since leaving Inter at the end of last season just weeks after winning the Serie A title -- his fourth Italian league triumph as a manager.
"We are delighted to announce the appointment of Antonio Conte as our head coach on a contract until the summer of 2023, with an option to extend," Spurs said in a statement.
"Antonio has won titles in Serie A, including a hat-trick of Scudettos with Juventus, the Premier League and also managed Italy, leading the Azzurri to the quarter-finals of Euro 2016."
Conte had been in advanced talks with Spurs in June about becoming Jose Mourinho's successor but they broke down after the two parties were at odds over key issues.
However, director of football Fabio Paratici is now in position at Tottenham and has a strong relationship with Conte, having worked with him at Juventus.
- 'Extremely happy' -
"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," said Conte.
"Tottenham Hotspur has state-of-the-art facilities and one of the best stadiums in the world.
"I can't wait to start working to convey to the team and the fans the passion, mentality and determination that have always distinguished me, as a player and as a coach."
The Italian said he was delighted the opportunity to manage Tottenham had returned.
"Last summer our union did not happen because the end of my relationship with Inter was still too recent and emotionally too involved with the end of the season, so I felt that it wasn't yet the right time to return to coaching," he said.
"But the contagious enthusiasm and determination of (chairman) Daniel Levy in wanting to entrust me with this task had already hit the mark. Now that the opportunity has returned, I have chosen to take it with great conviction."
Tottenham topped the Premier League table after three wins at the start of the season but the team are currently languishing in ninth position in the table after losing five of their past seven league games.
The Italian, who is expected to be given funds in January to strengthen the squad, is due to take training on Tuesday.
Conte's first game will be at home against Dutch side Vitesse Arnhem in the Europa Conference League on Thursday before Spurs play at Everton in the Premier League on Sunday.
Paratici said Conte's record "speaks for himself", referring to his vast experience and trophy-winning pedigree.
"I know first-hand the qualities Antonio can bring to us, having worked with him at Juventus, and look forward to seeing his work with our talented group of players," he said.
But Conte has a tough task on his hands to make Spurs leading contenders again.
The club, who have not won silverware since 2008, reached the Champions League final as recently as 2019 under former boss Mauricio Pochettino, who is now in charge of Paris Saint-Germain.
But they have lost their way since then and have missed out on the Champions League for two consecutive seasons.
Conte will be tasked with ensuring Tottenham play more adventurous football than the dour fare served up by the tactically conservative Nuno.
He will also have to get the best out of England captain Harry Kane, who has struggled to hit top form since his attempt to engineer a move to Manchester City was rebuffed by Levy.