Conte, who has signed a deal until 2023 with the option to extend, returns to the Premier League having won the division with Chelsea in 2017 and the FA Cup a year later. He also won Serie A during his spells at Juventus and Inter. Conte left Inter in May following their title success amid reports the club needed to cut costs because of the coronavirus pandemic.
"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," Conte said. "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.
"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.
"But the contagious enthusiasm and determination of 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."
The Italian was also approached to take over at Tottenham ahead of the 2021-22 campaign before Nuno was appointed. Other names in the frame following Jose Mourinho's exit included Paulo Fonseca, Mauricio Pochettino, Graham Potter, Gennaro Gattuso, Erik ten Hag, Brendan Rodgers and Julian Nagelsmann as Tottenham conducted a chaotic process to appoint a new manager.
Sources have told ESPN that Conte's readiness to revive discussions was the final factor pushing Tottenham into deciding to part with Nuno, who managed just 17 games in total. Nuno was sacked following Saturday's 3-0 Premier League home defeat to Manchester United.
Buongiorno Antonio... pic.twitter.com/26wgcdcYED— Tottenham Hotspur (@SpursOfficial) November 2, 2021
Managing director of football Fabio Paratici said: "We are delighted to welcome Antonio to the club. His track record speaks for itself, with vast experience and trophies in both Italy and England.
"I know firsthand 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."
Sources added that a number of senior players had lost faith in Nuno after a poor start to the season in which he became the first Spurs manager since Christian Gross in 1997 to lose five of his first 10 Premier League games in charge.
But it was the severity of the fan reaction to Saturday's loss that shocked senior figures at the club the most, leading them to consider Nuno's future the following day.
Information from ESPN correspondent James Olley was used in this report