The 21-year-old midfielder, who spent the first half of this season on loan at Parma, has signed a four-and-a-half-year contract with the Bundesliga club.
"Afriyie Acquah will be able to boost our first team greatly, even at a young age," Hoffenheim general manager Andreas Muller told Deutsche Pressagentur.
"He is a quality player and has the ambition to become even better. In addition, he plays in a position we have been looking to reinforce due to a list of injured players."
Acquah was linked with a move to Arsenal last month.