From the Miami International Airport, take LeJeune Road south to 836 West. Take the Florida Turnpike south towards Key West.
From the Fort Lauderdale Airport take I-595 west about 2 miles and take the Florida Turnpike south towards Key West. You will go through four tolls, $3 total to get to Florida City. If you miss the Florida Turnpike you can go another 6 miles, then take I-75 south, about 8 miles. After you pass the Miramar exit get in the right lane and take the turnpike south towards Key West.
The Florida Turnpike ends at US 1 in Florida City. Follow U.S. 1 south about 22 miles to Key Largo. Sanctuary Drive is near mile marker 100.