Marshall announced the resignation Saturday, a day after the Thundering Herd (5-7) finished the season with a 65-59 loss in double overtime at East Carolina.
Marshall allowed an average of 43 points per game this season.
Rippon spent three seasons at Marshall. He also had assistant coaching roles at Rutgers, Mississippi and Syracuse.
"I would like to thank Chris for all of his service to our program," Head Coach Doc Holliday said in the release. "We wish him and his family the best."
A search for his replacement is underway. Rippon declined comment, according to a university spokesperson.
The Thundering Herd had one of the worst statistical defenses in the Football Bowl Subdivision in 2012.
Entering Friday's loss to the Pirates, Marshall was ranked 97th in total defense and 116th in scoring defense. It finished the year averaging 43.1 points and 456.6 yards allowed in 12 games. Marshall finished the season at 5-7 despite having Conference USA's top offense in average yards (534.2 per game) and points (40.9 per game) gained.