Established in a region settled by Scots-Irish immigrants in the 1700s, Andrews was founded in 1909 by the merger of Harper's Crossroads and Rosemary. Named for founder Walter H. Andrews, the town initially bustled as it shipped local timber on the Seaboard Air Line Railroad. The boomtown atmosphere disappeared in 1929, when the railroad relocated most of its local operations, taking most of the town's residents with it. The population further decreased in 1932, when the Atlantic Coastal Lumber Company ceased local logging operations.

Timber operations continued on a smaller scale, however, and in 1971, the Seaboard Coastline Railroad (which had replaced the SALR) transferred passenger service to the newly-created Amtrack system. The historic Andrews train depot, which still serves Amtrack passengers, is a reminder of the town's boom days.

The nearby Andrews Town Hall Museum features a recreated Victorian Era home, furnished as it would have appeared in 1909, the year Andrews was founded. The Museum includes a period parlor, a kitchen, and a children's room, as well as a collection of railroad memorabilia. Today, Andrews is also known as the birthplace of comedian Chris Rock and the 1960s rocker "Chubby" Checker, who is credited for inventing the Twist dance craze.