In 2018, it was selected for preservation in the National Recording Registry by the Library of Congress as being "culturally, historically, or aesthetically significant".

[4] The music was written by George Cory, with lyrics by Douglass Cross, about two amateur writers nostalgic for San Francisco after moving to New York.

[6] Before Tony Bennett heard it, the song was pitched to Tennessee Ernie Ford, whom Claramae Turner suggested Cross take it to.

It then won the top prize of Grammy Award for Record of the Year, as well as for Best Male Solo Vocal Performance.

[11] The Songwriters Hall of Fame gave Bennett the Towering Performance Award for his vocal rendition of the song.

A slower-paced piano only version of the song appears as the intro theme to the Canadian television show Trailer Park Boys.

[16][17] At noon (PDT) on Saturday, April 25, 2020, in the midst of the COVID-19 pandemic and the shelter-in-place orders for people across the United States, San Francisco residents sang "I Left My Heart in San Francisco" in unison from their residences and other places of sheltering as a tribute to the spirit of the city and its fight to keep the virus in check.