The drive from Columbus to St. Louis is approximately 260 miles. You will typically take I-65 North to I-70 West. This is a major commute that typically takes 4 hours. St. Louis is a historic city on the Mississippi River known for the Gateway Arch.
Total Distance: 420 km driving, 370 km straight-line.
Traffic in St. Louis is very heavy; consider parking outside the city.
Any time, but avoid morning and evening rush hours in St. Louis.