William S. Gregory (August 4, 1825 – August 11, 1887) was the first mayor of Kansas City, Missouri in 1853.
When Kansas City was incorporated on March 18, 1853, it had an area 0.98 square miles (2.5 km2) and a population of 2,500. 63 votes were cast for mayor and Gregory defeated Dr. Benoist Troost by nine votes.
He was born in Shelby County, Kentucky.
Gregory moved with his wife Elizabeth to Jackson County, Missouri in 1844 from Kentucky and operated a grocery store on the levee. He and other settlers petitioned to incorporate the Town of Kansas. Gregory only served 10 months when it was discovered that he lived on a farm that was outside the city limits eastern boundary at Locust Street. Therefore, he was not eligible to be mayor.
He is buried in Elmwood Cemetery. In the 1930s 71st Street was renamed Gregory Boulevard in his honor.