The 23-year-old began his career with Ajax before joining United's youth set-up in 2014.
A versatile defender, Fosu-Mensah made his senior debut in 2016, eventually making 30 appearances for the club.
He will now get an opportunity to further his development in Bundesliga with Bayer.
Timothy Fosu-Mensah has joined Bayer 04 from Manchester United.
Welcome to the Werkself, Timothy! pic.twitter.com/L8amR13jxJ
— Bayer 04 Leverkusen (@bayer04_en) January 13, 2021