Costanzo was called up to the majors for the first time on May 12, 2012. In his first Major League at bat, he hit a sacrifice fly to left field, which scored Ryan Hanigan from third base. On May 19, 2012 Costanzo got his first Major League Hit off of New York Yankees pitcher Ivan Nova.
On June 6, he was optioned back to Triple-A Louisville. On August 1, Costanzo was designated for assignment.
On December 28, 2012, he signed a minor league deal with the Nationals.
Costanzo represented Team Italy in the 2013 World Baseball Classic.