Lee, who emerged from bureaucratic obscurity to become San Francisco's first Asian-American mayor more than seven years ago, died suddenly early Tuesday morning after suffering an apparent heart attack while grocery shopping.
Dr. Susan Ehrlich of Zuckerberg San Francisco General Hospital said Lee arrived at the hospital in critical condition shortly after 10 p.m. Monday.
Lee, 65, died of a heart attack, the San Francisco Examiner said.
Lee was the 43rd mayor of San Francisco and the first elected mayor of Chinese descent in a city steeped in Chinese American history.
Lee changed his mind and won a four-year term in 2011.
He leaves behind his wife Anita and his two daughters, Brianna and Tania. "Family, friends and colleagues were at his side", the mayor's office said in a statement.
Lee's ascension to Room 200 gave both Oakland and San Francisco Asian-American mayors at the same time.
But San Francisco assemblyman and former supervisor David Chiu disagrees.
Lee's office announced that Board of Supervisors President London Breed will serve as acting mayor.
As a law student, Lee represented residents of a public housing complex who sued San Francisco over unsafe and unsanitary conditions in the first tenants' rent strike against the city's housing authority, according to the Chronicle. This includes his city-centric sports view, which was always "What's good for the city is good by me".
Lee said his family's background as immigrants from China inspired his desire to fight Trump's anti-immigration stance.
California Senators Kamala Harris and Dianne Feinstein also issued sentimental statements on Mayor Lee's unexpected passing.
In 2015, he ran against a slate of little-known candidates who criticized him as doing more for tech leaders than for poor people. He graduated from Bowdoin College in Brunswick, Maine, in 1974 and from Boalt Hall School of Law at the University of California, Berkeley, in 1978. He worked as the executive director of the Human Rights Commission, became director of City Purchasing, and then in 2000 was appointed director of the Department of Public Works.