Known for most of its length as Gumboro Road, the state highway runs 5.08 miles (8.18 km) from U.S. Route 50 (US 50) just south of Pittsville north to the Delaware state line, where the highway intersects Delaware Route 26 (DE 26) and DE-MD 54.

MD 353 begins at an intersection with US 50 (Ocean Gateway) just south of Pittsville, heading northeast on two-lane undivided Sixty Foot Road, which continues south as a county highway past US 50.

After intersecting Main Street, the highway turns north past scattered residences.

After crossing Aydelotte Branch, MD 353 leaves Pittsville, crossing Burnt Mill Branch and passing through farmland all the way to the highway's northern terminus at the Delaware state line.

[5][6] On April 20, 2016, the portion of Sixty Foot Road between US 50 and MD 346 was transferred from county and town maintenance to state maintenance and became a southern extension of MD 353.