By 1966, Chiles left the Florida House to run for the Florida Senate. Despite 12 years in the Florida Legislature, Chiles was relatively unknown when he decided to bid for United States Senate in 1970. He embarked on a 1,003-mile walk from Pensacola to Key West for his campaign, earning him the nickname "Walkin' Lawton". It was successful and Chiles defeated his opponent William C. Cramer by a 53.9%-46.1% margin. Chiles retired from the United States Senate and from politics entirely in 1989.