The 33-year-old will join the Premier League side when his contract at Inter Milan expires at the end of June after agreeing a two-year deal.
Perisic worked with Spurs boss Antonio Conte at the San Siro, winning the 2020-21 Serie A title together, and turned down a new contract with the Italian club in order to head to London.
His arrival will mark a departure from Tottenham’s usual transfer policy of signing younger players with a sell-on value and is a further signal that they are giving their full backing to Conte.
Perisic is an experienced winner, having lifted league titles in Germany – with Borussia Dortmund and Bayern Munich – and Italy while also playing and scoring in a World Cup final for Croatia.
His versatility will appeal to Conte, who deployed him as a left wing-back at Inter, but he can also play as a winger, a second striker or attacking midfielder.
He leaves the San Siro after seven years with happy memories.
He posted on Instagram: “After 254 games, 55 goals, 49 assists, 3 trophies and 18,934 minutes spent on the pitch wearing this glorious jersey; my journey here has come to an end.
“Even though every end means a new beginning it’s important to reflect back on these past years and show you my deepest appreciation for the work accomplished.
“It was an unforgettable learning experience for me as a player and for my whole family.
“To the team, the staff, to all the employees but most importantly to the fans: you will always have a special place in my heart.
“I leave feeling privileged having this club in my portfolio.”
The signing is the start of what is expected to be a busy summer for Spurs in the transfer market as they try to build a squad that Conte feels is capable of challenging in the Premier League and Champions League.
Spurs are fully backing him and he will get the majority of the £150million that owners ENIC pumped into the club last week, as well as any proceeds raised from player sales.
Conte wants at least six new arrivals this summer as he overhauls the squad, with a number of players such as Harry Winks, Steven Bergwijn, Giovani Lo Celso and Tanguy Ndombele available to leave.
Perisic’s arrival may not be the only reunion this summer as Spurs are also understood to be interested in re-signing Christian Eriksen on a free transfer.
The Denmark international, who also worked with Conte at Inter Milan, is mulling over his future after a successful return to the Premier League with Brentford this season, just months after suffering a cardiac arrest on the pitch during Euro 2020.
Spurs have also agreed a deal to sign 34-year-old goalkeeper Fraser Forster on a free transfer from Southampton, the PA news agency understands.
Forster had a medical at the club last week and will sign a two-year deal, with an announcement set for later in the summer.