Colter threw for 199 yards and ran for 71 more with a touchdown to lead Northwestern to a 24-17 victory over Boston College.
Persa, a first-team All-Big Ten selection in 2010, had been limited in preseason practice as he continues to recover from Achilles tendon surgery. Colter saw more time with the first-team offense, but coach Pat Fitzgerald had been non-committal on who would start the opener.
Persa said this week that his Achilles is improving, but his mobility remains restricted.
Northwestern dropped its final three games last season after Persa ruptured his Achilles in a Nov. 13 win against Iowa.
Colter rushed for 105 yards and two touchdowns in the TicketCity Bowl against Texas Tech, but he completed just 3 of 9 passes for 38 yards with an interception last season.
Adam Rittenberg covers Big Ten football for ESPN.com. He can be reached at firstname.lastname@example.org. Information from The Associated Press was used in this report.