She was born in Franklin County, Missouri. At the age of 19, she married George Hearst, who later became a U.S. Senator. Soon after their marriage the couple moved to San Francisco, California, where Phoebe gave birth to their only child, William Randolph Hearst, in 1863.
A major benefactor of the University of California, Berkeley, she became the first woman Regent of the University of California, serving on the board from 1887 until her death. Also in 1887, she contributed to the establishment of the National Congress of Mothers, which evolved eventually into the National Parent-Teacher Association. In 1900, she co-founded the National Cathedral School in Washington, DC. A public elementary school near the National Cathedral School bears her name.
She was a member of the Bahá'í Faith. She briefly travelled to Akko and Haifa in Palestine (modern day Israel) on pilgrimage, arriving on December 14, 1889. She later wrote, "Those three days were the most memorable days of my life"
She died at her home in Pleasanton, California, aged 76, on April 13, 1919, during the worldwide influenza epidemic of 1918-1919, and was buried at Cypress Lawn Memorial Park, Colma, San Mateo County, California.