Prescott is a city in Pierce County, Wisconsin at the confluence of the St. Croix River and Mississippi River. The population was 4,258 at the 2010 census, making it the second-largest city in the county after River Falls, and the largest entirely within Pierce County.Prescott was home to the mother house of the Franciscan Servants of Jesus. The town was first settled by Philander Prescott, who opened a trading post there in 1839.