"The misconduct Mayor Bob Filner has been accused of is reprehensible and indefensible," Schultz said in a statement.
"I am personally offended by his actions and I firmly believe no employee should face a hostile environment or harassment at their place of employment. There is no place for this type of conduct in the workplace and certainly not in our city halls and public offices.
“For the good of the City of San Diego, I call on Mayor Filner to resign."
The move from the DNC comes a day after the county's Democratic Party called on Filner to resign amid piling-up accusations of sexual harassment and inappropriate behavior.
Just a week before, the county party was divided on whether he should resign. But over the past week, seven women have come forward with public allegations detailing accounts that include unwanted touching.
Schultz's call also came as the Republican Party mounted pressure on Democrats to denounce the actions of both Filner and New York City mayoral candidate Anthony Weiner, who has had new details about lewd online relationships revealed this week.
After Schultz's statement was released, RNC communications director Sean Spicer said, tongue in cheek, that it was a "profile in very delayed courage."