Alfred Schreuder will return ahead of the 2019-20 season to take over as head coach when Julian Nagelsmann leaves for RB Leipzig.
The 46-year-old, at present 2nd coach at Ajax, has agreed a three-year contract with the Bundesliga club, where he was assistant coach from October 2015 until January last year.
Schreuder will succeed Julian Nagelsmann, who will take charge of RB Leipzig after 2018-19.
"During my first spell, not just the club but the whole region became very dear to me, and I'm pleased, of course, that my family will join me on my return. I thank Ajax and, above all, sporting director Marc Overmars for their cooperation, understanding and fulfilment of my request for a change".
Hoffenheim sit ninth in the Bundesliga after 26 matches.