Driving or from area airports:
From Miami: Take the Florida Turnpike south until it ends in Florida City. Continue south on US1 to 80001 Overseas Highway.
From Orlando: Take the Florida Turnpike south to Fort Pierce and continue through Ft. Lauderdale, following signs for Homestead/Key West. Turnpike extension ends at Florida City on US1, which leads to Key Largo. Follow US1 to 80001 Overseas Highway.
From Tampa: Take I-75 south to Naples, and then across Alligator Alley to the Miami Exit and south to the Turnpike extension. Continue south on US1 to 80001 Overseas Highway.
The closest airports include Miami, Fort Lauderdale and minimal service through Key West.