SR 581, along with County Road 581 (CR 581), which extends 12.6 miles (20.3 km) to the south of SR 581's southern terminus, forms the major thoroughfare through New Tampa, a part of the city of Tampa annexed during the 1980s, to Wesley Chapel.
The portion of the road north of State Road 582 was renamed in 1984 from 30th Street by Hillsborough's Board of County Commissioners in honor of Bruce Barkley Downs, a deputy county administrator for public works.
North of Bougainvillea Avenue, the road passes by a Yuengling brewing plant and a more commercial area, heading towards State Road 582 (Fowler Avenue), where the name changes to Bruce B. Downs Boulevard and forms the western boundary of the University of South Florida.
Just north of the shopping centers, CR 581 passes through medical centers on both sides of the road, intersecting CR 582A (Fletcher Avenue), then leaving the medical area to residential areas, where the road starts to curve to the northeast, and enters a more sparsely populated area with newer developments.
It then has an interchange with I-75, continuing to the northeast and crossing into Pasco County, where it terminates at State Road 54 in Wesley Chapel.