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The Virginia and Tennessee Railroad built in the 1850s, ran completely through southwestern Virginia along the length of the Great Valley of Virginia. The railroad extended westward from Lynchburg, Virginia through a gap in the Blue Ridge Mountains near the town of Big Lick (present-day City of Roanoke); there, it turned southwestward and followed the Great Valley to Bristol, a total distance of 204 miles.

After the Virginia government refused to fund its construction, the City of Lynchburg incorporated the railroad on March 24, 1848 as the Lynchburg and Tennessee Railroad. Construction began in 1850, and on February 18, 1852, the railroad's first locomotive (the "Virginia") was tested when it climbed out of Lynchburg's James River basin.

After the American Civil War, the road was rebuilt, and came under the control of William Mahone, who was already leading the South Side Railroad and The Norfolk and Petersburg Railroad. He was named president of the V&T by the end of 1867. Mahone desired to consolidate the three roads, and build further west, and he worked for several years lobbying to get the needed legislation through the Virginia General Assembly.

In 1870, it became part of Mahone's Atlantic, Mississippi and Ohio Railroad. The letters A, M & O were said to stand for "All Mine and Otelia's." The Mahones lived in Lynchburg during this time, but moved to Petersburg in or before 1880.

The A, M & O was initially profitable, but fell victim to the Financial Panic of 1873, like many other southern railroads. Mahone was initially able to placate the English and Scottish bondholders, but the relationship soured in 1875. After several years of operating under receiverships, Mahone's role as a railroad builder ended in 1881 when northern interests purchased the A, M, & O and renamed it Norfolk and Western. Mahone was able to arrange for a portion of the State's proceeds of the sale to help found a school to prepare teachers to help educate black children and former slaves. The Virginia Normal and Collegiate Institute near Petersburg was forerunner of Virginia State College, which expanded to become Virginia State University.

Norfolk & Western Railway (N&W) was expanded west into the coalfields, and later into a much large system. 100 years later, the N&W was combined with the Southern Railway, another profitable carrier, to form Norfolk Southern Corporation (NS) in 1982.

Today, much of the former Virginia and Tennessee Railroad remains in service for Norfolk Southern (NS). The Fortune 500 company, headquartered in Norfolk, transports bituminous coal, intermodal shipping containers, automobile parts and completed vehicles, and other commodities in the 21st century global transportation markets.