Vertonghen, 33, has signed a contract which will see him remain with the Portuguese club until 2023.
The Belgian left Tottenham following the conclusion of their 2019/20 campaign in July after his contract expired, bringing an end to his eight-year stay in north London after making 300 appearances for the club.
The veteran fell down the pecking order under Jose Mourinho, featuring in just 23 Premier League appearances during his final campaign.
The defender left with the desire of a new challenge and to learn a new language, and will once again compete in the Champions League next season after Benfica finished second in the Portuguese Primeira Liga.
— SL Benfica (@SLBenfica)August 14, 2020
Speaking at his unveiling, Vertonghen said: "I came here to win trophies and I want to help the club to achieve those things. Becoming [Portguese] champion is definitely a goal I want to achieve."
He added: "If you look at the Benfica team now, it's great. It's one of the goals of the club to continue playing in the Champions League and I think we can definitely achieve that."
With the fan-favourite leaving, Tottenham wasted no time in repurposing his no.5 shirt, handing it to new signing Pierre-Emile Hojbjerg.
The midfielder is Tottenham's first signing of the summer and has received the backing of fellow Dane Christian Eriksen, who also played alongside Vertonghen at Ajax.
Vertonghen himself commented on Spurs' image of Hojbjerg's name on the shirt, tweeting: "This looks sooo weird!!"
Though he will be remembered for his crucial role in Tottenham's run to the Champions League final - playing a masterful role in their 3-0 round of 16 demolition of Borussia Dortmund - Vertonghen still made a telling contribution this season despite his limited role.
The Belgian scored a pivotal 91st-minute winner away at Wolves which - in hindsight - was crucial in their qualification for the Europa League, finishing above Nuno Espirito Santo's men only on goal difference.