Sessegnon, 20, was just 16 when he made his professional debut for Fulham four years ago and joined Spurs last year for 27 million euros ($31 million).
“I hope to gain experience in one of the best professional leagues in the world and I’m also looking forward to playing in European competition”, said Sessegnon with Hoffenheim having qualified for the Europa League.
He is under contract at White Hart Lane until 2025 but struggled for game time last season, making just 12 appearances for Tottenham, including six in the Premier League.
He had not played so far in 2020/21 under Spurs boss Jose Mourinho.
Sessegnon is seen as a “high-quality addition”, according to sports director Alexander Rosen to a Hoffenheim squad depleted by injuries to centre-back Ermin Bicakcic and left-back Konstantinos Stafylidis.