Jan Bert Lieve Vertonghen was formed at Germinal Beerschot and then Ajax, where he won three Eredivisie titles and was named Dutch Footballer of the Year in 2012. He spent eight seasons at Tottenham Hotspur, making more than 300 appearances, before leaving on a free transfer in 2020.

Benfica signed him on 14 August 2020 on a three-year contract at the age of 33. He debuted in a Champions League qualifier against PAOK on 15 September 2020 and made his league bow three days later in a 5-1 win over Famalicão, scoring his first goal for the club in the Europa League that December. Across two seasons he made 89 appearances, largely as a left-sided centre-back.

Vertonghen began 2022/23 outside Roger Schmidt's plans, with Nicolás Otamendi, António Silva and Morato preferred. On 2 September 2022 his contract was terminated by mutual agreement and he returned to Belgium with RSC Anderlecht. He captained Anderlecht from 2023/24 and retired in May 2025 as Belgium's most-capped international.