Chicago to Winston-Salem Road Trip Guide: Scenic Stops & Tips

When you set out from Chicago's Lake Shore Drive at 41.8827° N, you are following a historic corridor that pioneers used to cross the Ohio River into the heartland. The 668-mile drive to Winston-Salem at 36.0999° N takes you through a dramatic shift from Great Lakes flatlands to the rolling Piedmont, crossing the Eastern Continental Divide twice.

The route uses I-65 S from Chicago to Indianapolis, then I-74 E to Cincinnati, I-75 S through Kentucky, and finally I-40 E through Tennessee and North Carolina. Most drivers complete this trip in 10.5–11.5 hours of pure driving time, but savvy travelers plan for at least two overnights to truly experience the region.

For those wondering how long to drive Chicago, IL to Winston-Salem, NC, the answer depends on stops. Without breaks, it's a long day; with two nights, it becomes a rewarding journey. Is it worth driving Chicago, IL to Winston-Salem, NC? Absolutely—the changing landscapes, barbecue stops, and mountain views make it unforgettable.

Road quality on interstates is generally excellent, but I-40 through the Smokies has steep grades and curves. Construction zones in Indiana (2024) may cause delays. Keep a safe following distance on mountain descents.

• Pet-friendly framework: Most La Quinta and Motel 6 chains accept pets. State parks along the route like Brown County (IN) have dog-friendly trails.
• Family and child suitability: Indianapolis Children's Museum, the Newport Aquarium (Cincinnati), and the Great Smoky Mountains Railroad make great stops.
• Fatigue management & rest zones: Rest areas every 30 miles on I-65 with vending machines and clean restrooms. Use the 20/20/20 rule: every 20 minutes, look 20 feet away for 20 seconds.
• Hidden off-route spots: Madison, IN (historic river town); Clifty Falls State Park (waterfalls); and the Lost River Cave (boat tour).

Fuel economy varies: in the flat Indiana farmland, a sedan averages 30 mpg; through the Kentucky hills and Smoky Mountains, expect 26–27 mpg. Total fuel cost for the 668-mile trip at current US average gas price (~$3.50/gal) ranges from $75–$85 for a compact car. Diesel trucks will see about $95–$110.

For a deeper dive on planning stops, see how to find the best stops and hidden gems between cities. We recommend fueling up at TA Travel Centers or Love's, which are abundant every 30–50 miles on I-65 and I-40.

• Best stops Chicago, IL to Winston-Salem, NC include the Indianapolis Motor Speedway, the Ark Encounter in Kentucky, and the Blue Ridge Parkway entrance near Winston-Salem.
• Things to do between Chicago, IL and Winston-Salem, NC: Visit the Kentucky Bourbon Trail distilleries (off I-75), hike at Red River Gorge, or explore downtown Knoxville.
• Tolls: Only on the Chicago Skyway ($5.50 for passenger cars) and a small segment near Louisville no tolls. Cash and credit accepted.

From the Corn Belt of Illinois to the Cumberland Gap, the landscape transforms. South of Indianapolis, the terrain becomes gently rolling; by Kentucky, you see limestone bluffs and horse farms. The Appalachian Plateau near Knoxville offers dramatic ridges and tunnels.

The UNESCO World Heritage Sites near this route include the Mammoth Cave National Park (off I-65, 1.5 hours from Nashville) and the Great Smoky Mountains National Park (off I-40, 1 hour from Knoxville). Both are worth a detour.

• Climatic conditions: Summer temperatures range from 75°F in Chicago to 90°F in Winston-Salem; winter can bring snow in the Smokies. Best times: April–June and September–October.
• Culinary infrastructure: Must-try foods include Chicago deep-dish, Indiana pork tenderloin sandwiches, Kentucky hot brown, and North Carolina pulled pork barbecue. Family-friendly restaurants like Cracker Barrel and local diners are plentiful.
• Local commerce: Antique shops in small towns like Berea, KY, and Farmers' Markets in Asheville, NC (off I-40).