In the 1960s, the Port Authority began phasing out streetcar lines and replacing them with buses. The creation of a rail rapid transit system was also discussed, and one of the target routes was a corridor bordering Route 51 through the Brookline and Overbrook neighborhoods. While light rail would be developed during the following decade, the Port Authority decided to use the corridor to allows buses to avoid the crowded, narrow, and stop light-filled Route 51. In 1977, a two-lane route was constructed in a valley close to the road. Unlike later American busways, including the city's Martin Luther King Jr. East Busway (opened in 1983) and West Busway (opened in 2000), the route was not designed as a route in itself and does not feature the amenities associated with modern BRTs, such as branded buses, special stations, or other rail-like features. Instead, standard bus shelters are included and no routes terminate at the end of the busway. The main goal of the road is to allow for suburban buses to operate more quickly and to encourage the use of public transportation by allowing riders to avoid a highly congested highway. Following the naming convention of each busway being designated by a color, bus routes that use the South Busway begin with a "Y" for yellow.
The busway shared portions of its right of way with the city's light rail line. A section from the Glenbury to the South Bank stops was shared with the Overbrook line, and another section just after the Pioneer Avenue stop continues to share right of way from that point to South Hills Junction with the Beechview line. In 1993, the Overbrook line was suspended, and the right of way was exclusively busway. When the Overbrook line was rebuilt, it did not resume sharing the busway, rather, a new grade-separated private right of way was built parallel to the busway, and only the South Bank stop serving as the connection point between the rail line and busway.
Fourteen routes travel the busway, including 11 local routes and 3 rush hour flyer routes. Four of the local routes (39 Brookline, 40 Mt Washington, 43 Bailey, and 44 Knoxville) branch of off the busway to serve city neighborhoods, while the remainder rejoin with Route 51 or Route 88 to service suburbs.