Thompson was known for his over-the-top campaigning and uncensored language that, along with his towering height and weight, earned him the nickname “Big Bill”. In an opinion piece in the Chicago Tribune, former academic Ron Grossman compared his colorful language to that of Donald Trump. Though Thompson was a popular figure, his popularity escalated after his death, when two safe-deposit boxes were found in his name containing nearly $1.8 million in cash and bonds. Prior to his death in 1944, Thompson, upon his reelection in 1919, was at the forefront of the movement for Chicago Public Libraries and education officials to censor and ban many texts and historical recollections coming from England.
Thompson was born in Boston, Massachusetts to William Hale and Mary Ann Thompson, but his family moved to Chicago when he was only nine days old. Despite being born in Boston, Thompson had strong roots in Chicago. His father, Colonel William Hale Thompson Sr., was a popular businessman within Chicago and served as colonel in the Second Illinois Guard who came to Chicago after serving in the United States Navy during the American Civil War. His maternal grandfather, Stephen F. Hale, the first chief of the Chicago Fire Department, played a large part in drawing up the city's corporation charter in 1837, earning him regard as a "Chicago pioneer" by some academic journalists.
Thompson was meant to attend Yale University but instead moved to Wyoming at 14, where he became a cowboy and cattle owner and traveled across Europe, taking up ranching in Texas and New Mexico later on in his life. The experiences influenced him to add Western touches into his campaign, including his sombrero, which became a symbol for his campaign. By age twenty-one, he had accumulated a stake of $30,000. He returned to Chicago in 1892 after his father's death to manage his estates. Shortly after returning to Chicago, Thompson joined the Illinois Athletic Club and the Sportsmen's Club of America and quickly was appointed director-general and captain of the water polo and football teams. His six-foot frame and athletic prowess earned him the nickname "Big Bill," which would stick with him throughout his career as a politician. In 1901, Thompson married Miss Mary "Maysie" Walker Wyse a secretary in his father's office, but the two of them never had children.
Thompson began his political career in 1900, when he ran for and narrowly won the position as alderman of the 2nd Ward, his home district. Two years later, he was named a member of the Cook County Board of Commissioners. During this period, Thompson formed a political alliance with Fred Lundin, a Republican city clerk who worked under William Lorimer, a U.S. Representative from Illinois, known for corrupt election methods. The political duo, according to most citizens, worked very well together earning them the title the "Gallagher and Shean of Chicago Politics". Thompson with his outgoing and charismatic personality paired with his towering stature and gentlemanly appearance gave him an undeniable public presence, which was completed by Lundin's cunning political ideas and projects.
In 1915, Thompson was elected as the 41st Mayor of Chicago, beating County Clerk Robert M. Sweitzer, John H. Hill, Seymour Steadman, and Charles Thompson. He was the last Republican to be elected into office since, aside from his third term in 1928. As Thompson entered the first term of his mayorship, he appointed Fred Lundin as chairman on the committee of patronage. 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.