The portion of PA 501 between Lancaster and Lititz was chartered as the Lancaster and Lititz Turnpike in 1838, a private turnpike. The roadway between Lititz and Lexington was chartered as the Lititz and Lexington Turnpike in 1882. In 1894, the Lancaster and Lititz Turnpike was leased by the Lancaster Traction Company, which established a trolley line along the turnpike. This trolley line continued to operate until 1938. On October 7, 1926, both the Lancaster and Lititz Turnpike and the Lexington Turnpike were sold to the state and Lancaster County at $70,000 and $4,000, respectively.