This abandoned railway line was initially constructed by the South Side Railroad in the early 1850s; final completion of the line came in 1854. The line was originally intended to bypass Farmville, VA, for a more favorable low-profile grade route; however, Farmville, seeking the additional commerce a railroad can provide, partially subsidized the South Side Railroad to build through its town, which required a high-level crossing of the Appomattox River. (The originally-planned "low-grade" line was eventually built in 1916, and ultimately led to the abandonment of this route.)

In 1870, the South Side Railroad merged with other local railroads to form the Atlantic, Mississippi and Ohio Railroad, which continued operating the line. Shortly thereafter in the 1880s, the AM&O fell into bankruptcy and emerged as a new railroad entity known as the well-known Norfolk & Western Railroad. The line and the railroad came under the Norfolk Southern flag in 1982. In 2004, on the line's 150th anniversary, the line was abandoned due to both the high cost of maintaining the "High Bridge" over the Appomattox, and the newer "low-grade" line which offered easier (and thus cheaper) grades.

One notable feature of this line is the High Bridge at the Appomattox River. When construction was completed in October, 1853, it was considered "not the longest bridge in the world nor the highest, but the largest" at the time. The bridge played a strategic role during the U.S. Civil War, and was even the site of the Battle of High Bridge. The bridge was partially destroyed by fire during this engagement, and was rebuilt after the Civil War to its present length of 2400 feet, at a height 120 feet above the valley it crosses. Today, the bridge is a significant attraction and namesake of the High Bridge Trail State Park, which follows the abandoned Pamplin to Burkeville route through Farmville.