After Josiah's premature death from diabetes, William's father returned to Indiana, settling near other LaFollette relatives where he continued farming and built a flour mill.

William worked on the farm, clerked in a store, learned the jewelry business, and attended the local normal (public) schools.

The sixteen-year-old William headed west to the Washington Territory and took up farming in Whitman County, an area in the Palouse that had been off limits to settlers since the Indian Wars of the 1850s.

Later, he was extensively engaged as an orchardist at Wawawai on the Snake River, having purchased some 375 ac from his father-in-law, John Tabor (one of the founders of Whitman County) who had been among the first settlers to bring apples to the region.

[8] In order to educate his family, La Follette built a large home in Pullman to be near Washington State College.

[9][10] La Follette was a member of the World's Fair Commission and had charge of the Washington State building at the Chicago Exposition in 1893.

For much of the time he was in Congress, the two LaFollette families shared a large house that he had purchased in Mount Pleasant, Washington D.C.[16] The house became a center for debate and discussions of the great issues of the day as a steady stream of politicians, policy makers, academics, artists and labor and business leaders debated late into the night.

After the failed presidential bid and death of his cousin Robert, William La Follette returned permanently to the Palouse.

His son, William Leroy "Roy" LaFollette Jr., served for many years as Prosecuting Attorney for Whitman County (1922–1930, and again during World War II).