Interstate 385 (I-385) is an Interstate Highway located in The Upstate region of South Carolina. It goes from Clinton, South Carolina at Interstate 26 to Greenville, South Carolina at Laurens Road/U.S. 276 (Exit 42). After exit 42, Interstate 385 turns into a Business Spur and becomes East North Street and later â€” for northbound motorists only â€” Beattie Place. The spur promptly ends at U.S. 29 (Church Street) near the Bi-Lo Center in downtown Greenville.

The explosive economic growth of southern Greenville county is largely attributed to I-385 and its connection to the city of Greenville and the major cities of Atlanta and Charlotte (via I-85). This area is known by locals as the "Golden Strip".

I-385 features a rather unusual rest area in the median strip near Laurens, that serves both directions of traffic. It was completed as part of the original design of the U.S. 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 design is similar to many of those built on turnpikes that predated the Interstate System.

The general idea â€” but none of the specifics â€” of I-385 were present on the 1955 Yellow Book map of the Greenville area. Also of note is that Interstate 85 would have used the U.S. Route 29 corridor from Greenville east towards Spartanburg based on the diagram.

The portion of I-385 that replaced U.S. 276 (from SC-417 in Mauldin to SC-56 / I-26 in Clinton) was initially the first phase built of an SC DOT 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. As a result, I-26 was one of the first Interstates in the south to open in significant mileage (most in SC between 1959 and 1963).[citation needed]

Prior to 1985, I-385 was only signed as such from downtown Greenville to I-85. The portion of the freeway from U.S. 276 in Mauldin to the southern terminus at I-26 was signed as U.S. 276. When the connecting portion was completed, the entire freeway was signed as I-385.[citation needed]

For seven months ending July 23, 2010, northbound traffic could not use a 15-mile section of I-385 in Laurens County due to a $60.9 million project to pave the portion extending from South Carolina Highway 101 to the I-385-I-26 interchange near Clinton, SC in concrete. The closing of a major highway generated controversy. Closing the interstate for construction saved approximately $34 million.

Between 2002 and 2012, I-385 was widened from 2 to 3 lanes in each direction from just north of exit 24 near Fountain Inn to just south of Woodruff Rd/SC 146 (exit 35), with the portion between exits 31 and 35 resurfaced in concrete.