* Interstate 4 (I-4): Runs east-west across the state, connecting Tampa, Orlando, Daytona Beach, and Jacksonville.
* Interstate 95 (I-95): Runs north-south along the Atlantic coast, connecting Jacksonville, Daytona Beach, Fort Lauderdale, and Miami.
* Interstate 75 (I-75): Runs north-south through the center of the state, connecting Gainesville, Ocala, Tampa, Fort Myers, and Naples.
* Florida's Turnpike (FT): A toll road that runs north-south through the center of the state, connecting Homestead, Fort Lauderdale, Orlando, and Wildwood.
* Alligator Alley (I-75 and SR 29): A section of I-75 that runs east-west across the Everglades between Fort Myers and Naples.
* U.S. Route 1 (US 1): Runs north-south along the Atlantic coast, connecting Key West, Miami, Fort Lauderdale, West Palm Beach, Vero Beach, and Jacksonville.
* U.S. Route 27 (US 27): Runs north-south through the central part of the state, connecting Miami, Clewiston, Sebring, and Tallahassee.
* U.S. Route 41 (US 41): Runs north-south along the Gulf Coast, connecting Miami, Fort Myers, Naples, Sarasota, Tampa, St. Petersburg, and Ocala.
* U.S. Route 98 (US 98): Runs east-west across the state, connecting Pensacola, Panama City, Tallahassee, Live Oak, and St. Augustine.