West Middlesex is a borough along the Shenango River in southwestern Mercer County, Pennsylvania, United States. The population was 815 at the 2020 Census. It is part of the Hermitage micropolitan area.

The Shenango River is a principal tributary of the Beaver River, approximately 100 mi (160 km) long, in western Pennsylvania in the United States. It also briefly flows through small portions of northeastern Ohio. Via the Beaver and Ohio Rivers, it is part of the watershed of the Mississippi River.