Because this is the second time the 26-year-old has been removed from the 40-man roster in his career, Pena has three days to decide whether to accept the assignment or elect to become a free agent.
Pena allowed three consecutive home runs en route to surrendering five runs in 1 2/3 innings in Monday's Opening Day loss to San Francisco.
Acquired by the Brewers in the trade that sent Zack Greinke to the Los Angeles Angels in July 2012, Pena went 2-1 with 4.28 ERA in five starts and one relief appearance for Milwaukee in 2015.
Andrew Gruman is a contributor to MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.