The county Democratic party's central committee voted 34-6 for his resignation Thursday.
The committee had deadlocked on the issue last week, saying there was not enough evidence to call for his resignation because the allegations had come from anonymous women.
The party strongly supported Filner in his campaign for mayor last year to replace Jerry Sanders, who was term limited.
Seven women have come forward to publicly accuse the mayor of sexual harassment. Four of whom spoke for the first time Thursday night on public television.
The first lawsuit alleging sexual harassment was filed this week against Filner by the mayor's former communications director, Irene McCormack.
Two other women, San Diego Democratic political consultant Laura Fink and San Diego Unified School District psychologist Morgan Rose, accused Filner of making unwanted physical contact with them.
The women who came forward Thursday are a retired U.S. Navy Rear Admiral, the president of the San Diego Port Tenants Association, a local businesswoman and the San Diego State University Dean. Each said Filner made unwanted sexual advances toward them at public events.
Filner shows no signs of backing down. He attended two press conferences, answering questions evasively saying things such as "Let the legal process work itself out."