The business route promptly ends at US Highway 29 (US 29; Church Street) near Bon Secours Wellness Arena in downtown Greenville.

It was completed as part of the original design of the US 276 expressway in 1958, modeled after the type of single median-located rest areas shared by both north and southbound traffic (to save money).

The portion of I-385 that replaced US 276[2] (from South Carolina Highway 417 [SC 417] in Mauldin to SC 56/I-26 in Clinton) was initially the first phase built of a South Carolina Department of Transportation (SCDOT) plan that predated the Interstate System to upgrade and bypass existing through routes, the goal of forming a single limited-access highway from Greenville to the port of Charleston via the state capital of Columbia.

This plan was scrapped as soon as the future I-26 was added to the act of Congress that set into motion the Interstate System.

[citation needed] For seven months ending July 23, 2010, northbound traffic could not use a 15-mile (24 km) section of I-385 in Laurens County due to a $60.9-million (equivalent to $83.1 million in 2023[3]) project to pave the portion extending from SC 101 to the I-385/I-26 interchange near Clinton in concrete.

[8] Signage previously existed for this spur route but, by 2007, has been removed;[citation needed] appears only in the SCDOT Greenville–Spartanburg Metro map.