Stanzi was 14–4 in his career as Iowa's starter going into his senior season, and in July 2010, Stanzi was named to the 2010 Davey O'Brien National Quarterback Award and Manning Award watch lists. He was also a finalist for The 2010 Premier Player of College Football Trophy which is awarded based on fan votes.
Stanzi returned to Iowa in 2010 with 9 touchdowns and no interceptions through his first four games. He completed 19-of-25 passes with three passing touchdowns on September 24, 2010.
One of Stanzi's most memorable moments of the 2010 season occurred on November 6 in a game against Indiana, in which he connected with Marvin McNutt for a 52-yard touchdown which put Iowa up 18–13 with 2:56 remaining in the game. Stanzi put up big numbers in the 2010 season with a 167.2 quarterback rating along with 22 touchdowns. Stanzi ranked third in the nation in passing efficiency.
Stanzi graduated from Iowa in December 2010 with a B.A. in interdepartmental studies from the College of Liberal Arts and Sciences.