Bill Knowland was the son of Joseph R. Knowland, who served as a member of the United States House of Representatives for California, and would in time succeed his father as editor and publisher of the Oakland Tribune. The family fortune derived from his grandfather, Joseph Knowland senior, who had built up a lumber business.
Knowland achieved much at a young age. He made campaign speeches for the 1920 Republican National ticket of Warren G. Harding and Calvin Coolidge at the age of twelve, married at nineteen, became a California State Assemblyman at twenty-five, entered the United States Senate at thirty-seven, and became a grandfather at forty-one. At the University of California at Berkeley he took a three-year accelerated degree program in political science (Zeta Psi), graduating in 1929.
In November 1932 he was elected to the California State Assembly, and in 1934 to the State Senate, deciding not to seek re-election in 1938. From 1940-42 he served on the executive committee of the Republican National Committee. In June 1942 he was drafted and rose to the rank of major. In 1945 he was appointed to the United States Senate on the death of Hiram Johnson. He was highly critical of the Truman administration and supportive of the struggle of Chiang Kai-Shek against Mao Tse-Tung and the Chinese Communists.
In 1953, he became Senate Majority Leader and then from 1955 Minority Leader. In 1958 he surprised many by deciding to run for Governor of California. He secured the nomination following a bruising contest, but his endorsement of Proposition 18 – which would have enacted a right-to-work act – proved his undoing, and he was soundly defeated at the polls. He never ran for elective office again, and in order to pay his campaign debts his father had to sell the Oakland Tribune radio station, KLX. He was titular head of the California Republican Party until 1967, when he was succeeded by Ronald Reagan.
After the death of his father in 1966, Knowland took over the Oakland Tribune and saw it through its centenary in February 1974. However, by that time he was heavily in debt and his second marriage had failed after only a brief time. He died later that month from a self-inflicted gunshot wound. In 1977 the Knowland family sold its interests in the Oakland Tribune.
He was twice married and had three children and two stepchildren.