Born in Newton, Kansas, Unruh served in the U.S. Navy during World War II. After the war, he enrolled at the University of Southern California, receiving a B.A. in Political Science and Journalism in 1948.
Unruh's political career began as an unsuccessful candidate for the California State Assembly in 1950 and 1952. He was elected as a member of the Assembly on his third attempt in 1954. In 1956, he was an unsuccessful candidate for Presidential Elector on the Democrtic ticket for California. During 1959, he authored California's Unruh Civil Rights Act, which outlawed discrimination for housing or employment and was a model for later reforms enacted nationally during the 1960s and 1970s. Unruh was Speaker of the California State Assembly from 1961 to 1969 and a delegate to Democratic National Convention from California in 1960 and 1968.
He became a national figure in Democratic Party politics, often feuding with fellow Democrat Pat Brown, who was Governor of California from 1959 to 1967, and was a case-study in the James Q. Wilson treatise on machine politics, The Amateur Democrat.
As an early supporter of the 1968 Presidential campaign of Robert F. Kennedy, Unruh emerged as a pivotal figure before the Democratic Convention. He helped Kennedy capture the California Primary in June, but an assassin's bullet that same night ended Kennedy's life. In the confusion that followed, Unruh helped keep suspect Sirhan Sirhan from the reach of angry Kennedy supporters. After an unsuccessful effort, led by Unruh and Mayor Richard J. Daley of Chicago, to draft Senator Edward M. Kennedy, he finally endorsed Eugene McCarthy at the 1968 Democratic Convention in Chicago.
Unruh left the legislature to run for Governor against Ronald Reagan in 1970, then was a candidate for Mayor of Los Angeles in 1973. He lost both elections, but was elected State Treasurer in 1974, and served from 1975 until his death from prostate cancer on August 4, 1987.
The University of Southern California Department of Political Science includes the Jesse M. Unruh Institute of Politics.
According to an apocryphal tale, Unruh was nicknamed "Big Daddy" by Raquel Welch, when the two were allegedly romantically involved. Welch denies the claim. It is more likely that the nickname comes from a character in the Tennessee Williams play, Cat on a Hot Tin Roof.