It takes US 17 and SR 15, from the Duval county line just south Interstate 295, until its northern end at Willow Branch Avenue, with the road itself becoming one of the incarnations of College Street in the Riverside area of Jacksonville.

The highway intersects east–west connector Collins Road and continues along the east edge of a railroad, the CSX A line for most of its length.

Immediately north of Collins Road, the highway serves as the western border of Naval Air Station Jacksonville along the St. Johns River, with three gates, though two are rarely used.

North of Plymouth Street, the US 17 highway curves in a northeastern direction after rounding the FSCJ Kent campus, and just north of Wolfe Street, the Roosevelt Expressway splits off from Roosevelt Boulevard between the Murray Hill and Avondale neighborhoods, where the highway features an interchange at South Edgewood Avenue.

[1] Before this route was legislated in 1939, Clay County traffic into the City of Jacksonville made use of a combination of several smaller, narrower roads along the west bank of the St. Johns River.