Knoxville was on Southern Railway's main line from Bristol through Chattanooga to Memphis. Another main line from Asheville joined the main line from Bristol at Morristown. Another important line diverged from the main line west of the station north to Harriman, where it connected with SR's Cincinnati New Orleans & Texas Pacific subsidiary extending north to Cincinnati. At K&A Jct., 1/2 mile west of the station, the K&A Branch diverged south to Maryville.
An additional Southern Railway line had branched from the main line north at Coster, extending northeast to Cumberland Gap. But much of that branch in the area more importantly became part of the "Beverley Cut-Off", connecting Sevier Yard to the east, with the main line north.
The Louisville & Nashville station in Knoxville was on a spur, extending 1 mile northeast from West Knoxville, on the main line between Cincinnati and Atlanta.
The Smoky Mountain Railroad served Knoxville via Southern Railway's K&A Branch, with a station at Main Street. The SMR line diverged from the SR line at Vestal, 2 miles south of the station.