The majority, between Dothan and Huntsville, is signed as U.S. Route 231 (US 231), but the two ends – south to Florida and north to I-65/US 31 near Tennessee – are independent.

In those areas, US 231 uses SR 1, sharing the route with US 431 north of Huntsville, where it is referred to as Memorial Parkway.

An 18-mile-long (29 km) stretch of SR 53, from Research Park Boulevard in Huntsville to just south of Ardmore, is designated as the "Paul Luther Bolden Memorial Highway" in honor of Paul L. Bolden, a Medal of Honor recipient and Madison County's most-decorated World War II veteran.

Between Dothan and Huntsville, SR 53 is the unsigned partner to US 231, however, only SR-53’s mile markers are present along the route.

At Huntsville, SR 53 diverts from US 231 and once again becomes a signed route until it reaches its northern terminus just west of Ardmore at I-65/US 31 crossing several major roads along the way including University and Sparkman Drives in Huntsville.