Joseph I. Castro resigned on Thursday, effective immediately, said the CSU Board of Trustees.
In a statement, Castro called it the most difficult decision of his professional life.
The move comes amid reports that Castro, while president of Cal State Fresno, didn't properly follow up on years of complaints of sexual harassment and other complaints against a top official who was allowed to retire.
Steve Relyea, CSU's executive vice chancellor and chief financial officer, will be acting chancellor until an interim chancellor has been named, the Board of Trustees said.
The Cal State system is the largest four-year university system in the country with 23 campuses, 477,000 students and 56,000 faculty and staff, according to its website.
Castro, appointed in 2020, was the first Mexican American and native Californian to lead the CSU system.
"I have been honored to serve the California State University for more than eight years, including as its eighth chancellor, and the decision to resign is the most difficult of my professional life," Castro said in a statement. "While I disagree with many aspects of recent media reports and the ensuing commentary, it has become clear to me that resigning at this time is necessary so that the CSU can maintain its focus squarely on its educational mission and the impactful work yet to be done."