Borussia Monchengladbach officially unveiled Blessin as their new head coach, with the Bundesliga's bottom club confirming the 53-year-old has signed a contract until 2028.
He succeeds the recently sacked Eugen Polanski at the Niederrhein club.
Assistant coach Jan-Moritz Lichte had been in interim charge for the weekend's game against FSV Mainz 05, but could not help Gladbach to their first points of the season in a 4-3 defeat. Gladbach remain without a win after five league games.
A significant upturn is now expected of Blessin, who is well versed in relegation battles in the German top flight. The Stuttgart-born coach spent almost two years in charge of FC St. Pauli, a role that ended at the start of June, and led the Hamburg club through their own fight against the drop in the Bundesliga.
Before that, he managed Union Saint-Gilloise in Belgium, winning the domestic cup, as well as Genoa in Serie A and Belgian side KV Oostende, having started his coaching career with RB Leipzig's youth teams.