State Route 157 is a 76-mile (122 km) long route in the northern and northwestern part of the state. The southern terminus of the route is at the junction with U.S. Highway 278 approximately ten miles east of Cullman, and the northern terminus of the route is at the Tennessee state line northwest of Florence. SR-157 continues as Tennessee State Route 227 once it crosses into Tennessee.

State Route 157 is oriented in a northwestward trajectory from its originating point. This orientation continues for the duration of the route. While the route does not pass through the city limits of Cullman, it serves as a northern bypass of the city that enables motorists on westbound US-278 a quicker and more direct access to northbound Interstate 65.

West of I-65, SR-157 serves as a connecting route between Cullman and Florence. This segment of the route is designated as the University of North Alabama Highway, in reference to the institution of higher learning located in Florence.

SR-157 has been four-laned along almost its entire length. This project, which began in the 1980s, was finally completed in the summer of 2007.