The most utilized access to Everglades National Park is via the park headquarters entrance southwest of Homestead and Florida City. If you're coming to the Everglades from Miami, take Route 836 West to Route 826/874 South to the Homestead Extension of Florida's Turnpike, U.S. 1, and Krome Avenue (Route 997/old U.S. 27). To reach the Ernest F. Coe Visitor Center from Homestead, go right (west) from U.S. 1 or Krome Avenue onto Route 9336 (Florida's only four-digit route) in Florida City and follow signage to the park entrance.

Route 9336 travels 38 miles from the Ernest F. Coe Visitor Center southwest to the Florida Bay at Flamingo. It crosses a section of the park's eight distinct ecosystems: hardwood hammock, freshwater prairie, pinelands, freshwater slough, cypress, coastal prairie, mangrove, and marine-estuarine. Route highlights include a dwarf cypress forest, the transition zone between saw grass and mangrove forest, and a wealth of wading birds at Mrazek and Coot Bay ponds—where in early morning or late afternoon you can observe them feeding. Be forewarned, however, that flamingo sightings are extremely rare. Boardwalks, looped trails, several short spurs, and observation platforms help you stay dry. You may want to stop along the way to walk several short trails (each takes about 30 minutes): the wheelchair-accessible Anhinga Trail, which cuts through saw-grass marsh and allows you to see lots of wildlife (be on the lookout for alligators and the trail's namesake water birds: anhingas); the junglelike—yet, also wheelchair-accessible—Gumbo-Limbo Trail; the Pinelands Trail, where you can see the park's limestone bedrock; the Pahayokee Overlook Trail, ending at an observation tower; and the Mahogany Hammock Trail with its dense growth. Before heading out on the trails, inquire about insect and weather conditions to plan accordingly, stocking up on bug repellent, sunscreen, and water as necessary. Even on seemingly sunny days, it's smart to bring rain gear.