The Lancaster & Chester bridges between two former Southern north-south lines, once running through Lancaster (that is now truncated there, with a portion of the line on south owned by the L&C), and one running through Chester. At Lancaster the line departs on the south side of the former Southern, heading west-southwest, curves around to the northwest, and then turns west-southwest again, descending into the Cooper River valley past Grace, bridging over the river at Elliot, and climbing out of the valley on the west side, past Fort Lawn, where there was once a flat crossing with an SAL branch.
The railroad runs along the south side of SR 8, between the road and the front lawns of an industrial park, as it turns curvily west, curvily west-northwest past Bascomville, spurs on the south side to the L&C Distribution Center and to Thyssen Steel, and curvily west past Richburg, Knox, Orrs, where a spur to GAF heads north, and Warwick, before turning north to join the other ex-Southern line at Chester.