Wicomico County is located in the southeastern part of the U.S. state of Maryland, on the Delmarva Peninsula. As of the 2020 census, the population was 103,588. The county seat is Salisbury. The county was named for the Wicomico River, which in turn derives its name from the Algonquian language words wicko mekee, meaning "a place where houses are built," apparently referring to a Native American town on the banks. The county is included in the Salisbury, MD-DE Metropolitan Statistical Area.

Maryland's 1st congressional district encompasses the entire Eastern Shore of Maryland, including Salisbury, as well as Harford County and parts of Baltimore County; it is the largest congressional district in the state geographically, covering 11 counties.