The 24-year-old Di Santo, who has won two caps for Argentina, joined as a free agent after spells in England at Chelsea, Blackburn Rovers and Wigan.
"We were looking for a robust forward who had experience in the big leagues. We are certain to have found a good solution with Franco," said Werder sports director Thomas Eichin.
"He wants to go with Argentina to the 2014 World Cup and we would be happy if he could make himself noticed here at Bremen to reach his goal."
The former Bundesliga powerhouse is eager to return to winning ways after spending much of the past few seasons in the lower half of the table.
The arrival of Di Santo could also spell the end of Marko Arnautovic's stint at the northern club with the Austrian out of favour since last season.
Werder, who won their opening league game 1-0 at Eintracht Braunschweig last week, host Augsburg on Saturday.