Chief Greg Suhr stepped down from his job as the city's top cop at the request of Mayor Ed Lee.
Suhr, 57, had already been under pressure to resign in the wake of two racist and homophobic texting scandals
and controversial shootings of minority suspects by his officers.
His opponents have held protests and hunger strikes in an effort to force him to resign. Pressure mounted when four members of the Board of Supervisors joined in the calls for his resignation.
The mayor had stood by Suhr for months, but that changed following the Thursday morning shooting and a subsequent meeting between the two men.
"I have arrived at a different conclusion to the question of how best to move forward," Lee said in a prepared statement released Thursday afternoon. "That's why I have asked Chief Suhr for his resignation. And in the best interest of the City he loves so much, he tendered his resignation earlier today."
Suhr could not be reached for comment Thursday evening.
Lee named Deputy Chief Toney Chaplin the acting chief. Chaplin, who oversees the department's Professional Standards and Principled Policing Bureau, is African-American.
The mayor praised the outgoing chief as "a model San Franciscan and a great man."
"He will always have my respect," Lee said.
Police union leader Martin Halloran, who worked alongside Suhr for years, praised "his integrity, morals and his deep commitment to the mission of public safety."
"His retirement under pressure is an extreme loss to the department and the city, " Halloran said.
"Chief Suhr, at the core, was and always will be a cop's cop and dedicated to the men and women who don the uniform every day to serve and protect," he said.
The mayor said his decision was influenced both by recent events, as well as chronic tension between the police and minority communities in the city.
"The past several months have shaken and divided our City, and tensions between law enforcement and communities of color that have simmered for too many years have come into full view," the mayor's statement read. "These officer-involved shootings, justified or not, have forced our City to open its eyes to questions of when and how police use lethal force."
He mentioned the most recent shooting that occurred Thursday morning in the predominantly African-American Bayview District. A woman in what police said was a stolen vehicle was fatally shot by a San Francisco police sergeant. It is unclear whether the woman was armed.
The woman was identified as Jessica Williams, 29, the city's medical examiner's office said Saturday.
The shooting remains under investigation.
"Though the facts are still emerging," the mayor said, "the community is grieving, and I join them in that grief."
One incident that has drawn widespread attention -- and criticism -- is the fatal police shooting of Mario Woods
in December. Woods was armed with a knife when officers opened fire. The confrontation was captured on a cell-phone video. Critics of the police say Woods was too far away to represent a threat requiring deadly force. The shooting remains under investigation.
John Burris, a prominent civil rights attorney who represents the Woods family, called Suhr's resignation "the end of an era."
"He was old school. He could not and did not make the changes necessary. Fresh eyes were needed," Burris said in an interview with CNN. "Hopefully, they can bring in someone as chief who understands reform and who can implement the changes that will be necessary to get the department in top shape."
Jeff Adachi, San Francisco's public defender, who has long butted heads with the SFPD, said he would greet Chaplin with an open mind.
"I'm looking forward to hearing his ideas -- his vision for the department," Adachi said, "how to take the department forward and how to truly transform the culture that is killing people."
Criticism of the department began to build in April after CNN obtained racist and homophobic text messages that were traded among a handful of officers.
They contained references to a "nig" and "beaners" and compared African-Americans to wild animals.
Suhr held two press conferences within a week attempting to assure the public that he had zero tolerance for such language and was taking steps to ensure every officer in the department shared that view.
In his statement, Lee said the department has made meaningful progress in its reform efforts.
"But it hasn't been fast enough," he said. "Not for me, not for Greg."