Known as "Big Bill", Thompson was the last Republican to serve as Mayor of Chicago. Thompson was born in Boston, Massachusetts, but his family moved to Chicago when he was only nine days old. Instead of college, he traveled in Europe and then took up ranching in Texas and New Mexico, returning to Chicago in 1892 after his father's death.
Early in his mayoral career, Thompson began to amass a war chest to support an eventual run for the Presidency by charging city drivers and inspectors $3 per month. He was mayor during the Chicago Race Riot of 1919 and was said to have control of the 75,000 African-American voters in his day. Always a flamboyant campaigner, during the 1923 election, Thompson held a debate between himself and two live rats which he used to portray his opponents. After being defeated in 1923, Thompson organized a "scientific" expedition to search for tree-climbing fish in the South Seas.
In 1927, Al Capone's support allowed Thompson to return to the mayor's office. Pledging to clean up Chicago and remove the crooks, Thompson instead turned his attention to the reformers, whom he considered the real criminals. According to Thompson, at this time the biggest enemy the United States had was King George V of England. Thompson promised his supporters that if they ever met, Thompson would punch the king in the nose. During this final term in office, the "Pineapple Primary" occurred (April 10, 1928), so-called because of the bombs used to intimidate politicians. The St. Valentine's Day Massacre also took place while Thompson was mayor. Thompson blamed Ruth Hanna McCormick's disloyalty for his loss at the 1928 Republican National Convention, and he returned the favor during her 1930 campaign for the United States Senate. Thompson had had a longstanding rivalry with the McCormicks. He had a distaste for Robert Rutherford McCormick who published the Chicago Tribune. Widow McCormick's former husband, Joseph Medill McCormick, was the publisher's brother.
Amid growing discontent with Thompson's leadership — particularly in the area of cleaning up Chicago's reputation as the capital of organized crime — he was defeated in 1931 by Democrat Anton Cermak. Cermak was an immigrant from Bohemia, and Thompson used this fact to belittle him with ethnic slurs such as:
Cermak replied to these with, "He doesn't like my name....It's true I didn't come over on the Mayflower, but I came over as soon as I could," which was a sentiment to which ethnic Chicagoans could relate and Thompson's slurs largely backfired.
After Thompson's defeat, the Chicago Tribune wrote that
Upon Thompson's death, two safe deposit boxes in his name were discovered to contain nearly $1.5 million in cash.