Helfrich replaces Chip Kelly, who last week was hired to lead to the Philadelphia Eagles.
"We were looking for a coach who exemplifies excellence, leadership and character, and who would embrace what our winning football culture is all about," Oregon Athletic Director Rob Mullens said. "We found that person in Mark."
Helfrich, 39, has served as the Ducks' offensive coordinator since 2009.
"As a lifelong Duck fan, this is a responsibility that I welcome and accept the undertaking that stands before me to carry on the legacy of success that has been created by my many predecessors," the Oregon native said.
Helfrich was among at least two candidates interviewed for the position, sources told The (Portland) Oregonian. The other was Stanford offensive coordinator Pep Hamilton.
His hiring is expected to provide continuity for the Ducks' prolific offense, which averaged 49.6 points per game under Kelly.