From Orlando:
Take I-4 West towards Tampa. Merge on to Florida Turnpike exit 77 South toward Miami. Portions toll. Merge on to US-1 South. Take US-1 South to Key West. Turn right on Duval Street. Take Duval to Front Street and turn right.

From Tampa:
Take I-75 South exit 15A toward Naples. Portions toll. Take the Turnpike South exit. Exit 5. Merge on to Florida Turnpike South. Portions toll. Stay straight and merge on to US-1 South to Key West. Turn right on Duval Street. Take Duval to Front Street and turn right.

From Ft. Lauderdale/Miami:
Begin on I-95 South. Interstate 95 becomes US-1 South. Merge on to Florida Turnpike. Portions toll. South towards Key West. Stay straight and merge on to US-1 South to Key West. Turn right on Duval Street. Take Duval Street to Front Street and turn right.