Johnson was born in Sacramento, California, his father was Grove Lawrence Johnson, a Republican Representative and state legislator famous for his support of personal interests.

After attending private schools, he first worked as a shorthand reporter and stenographer in law offices. He eventually decided on a legal career, studying at the University of California, Berkeley. He was admitted to the Bar in 1888 and commenced practice in his hometown. In 1902 he moved to San Francisco. He served as Assistant District Attorney and became active in reform politics, taking up an anti-corruption mantle. He attracted statewide attention in 1908 when he served as the prosecution in a notorious graft-trial case, his success due to the fact that his predecessor had been gunned down in the courtroom. He married Minne L. McNeal; the couple had two sons.

In 1910 he won the Gubernatorial election as a member of the 'Lincoln-Roosevelt' Party, a liberal Republican movement running on an anti-Southern Pacific Platform. He toured the state by horse. In office, Johnson was a populist who implemented several reforms. Among these were the popular election of U.S. Senators, relief for women's suffrage and campaign reform to allow candidates to register in multiple parties.

Nationally, Johnson was a founder of the Progressive Party in 1912. That same year, he was the Vice Presidential candidate on the ticket with former President Theodore Roosevelt; his selection helped Roosevelt to carry California by 0.2f the votes cast, but the Progressives lost the election to Woodrow Wilson.

Johnson was re-elected governor in 1914 and in 1916 ran successfully for the U.S. Senate, taking office on March 16, 1917. It was this year that he spoke the words that he is best remembered for today: "the first casualty when war comes, is truth".

Following Roosevelt's death in January 1919, Johnson came to be regarded as the natural leader of the Progressive Party in the United States. In 1920 he was defeated for the Republican Presidential nomination by Warren Harding. He received ten votes for the nomination against Calvin Coolidge in 1924. As Senator, Johnson proved extremely popular - in 1934 he was re-elected with 94.5f the popular vote.

During the Presidency of Franklin Roosevelt Johnson supported his economic recovery package the New Deal and frequently crossed the floor to aide the Democrats, although he never switched party affiliation. He achieved Senate seniority as Chairman of the Committee on Cuban Relations in the Sixty-sixth Congress; he was also a member of the Patents, Immigration, Territories and Insular Possessions and Commerce Committees.

Having served in the Senate for almost thirty years, Johnson died in Bethesda, Maryland, on August 6, 1945. News of his death, however, was overshadowed by the nuclear bomb attack on Hiroshima, Japan, which occurred that same week. He was interred in Cypress Lawn Memorial Park in Colma, California.