Lake City sits at the junction of I-10 and I-75 — one of the most prominent highway crossings in the South. By car it is about an hour west of Jacksonville and 90 minutes north of Gainesville. Atlanta is roughly three and a half hours to the north via I-75.
Lake City Gateway Airport (LCQ) handles small general aviation and charter flights but has no scheduled commercial service. The nearest commercial airports are Jacksonville International (about 60 miles east) and Gainesville Regional (about 60 miles south).
Greyhound operates bus service through Lake City with connections to Jacksonville, Gainesville, and Tallahassee.