The city encompasses Key West, the namesake island, the part of Stock Island north of U.S. 1 (the Overseas Highway) (east), Sigsbee Park (north, originally known as Dredgers Key), Fleming Key (north), and Sunset Key (west, originally known as Tank Island). Nearby Key Haven (northeast), the part of Stock Island south of U.S. 1 (east), and Wisteria Island, better known as Christmas Tree Island (northwest), are in unincorporated Monroe County. Both Fleming Key and Sigsbee Park are part of the NAS Key West and are inaccessible by civilians.

Key West is known as the Southernmost City in the Continental United States. It is also the southern terminus of U.S. 1, State Road A1A and the East Coast Greenway

.Key West is 129 miles (207 km) southwest (229.9 degrees) of Miami, Florida, (about 160 driving miles) and 106 miles (170 km) north-northeast (21.2 degrees) of Havana, Cuba. Cuba, at its closest point, is 94 statute (81 nautical) miles south.

Key West is a seaport destination for many passenger cruise ships. The Key West International Airport provides airline service. Hotels and guest houses are available for lodging.Naval Air Station Key West is an important year round training site for naval aviation due to the superb weather conditions. It is also a reason the city was chosen as the Winter White House of President Harry S. Truman.

The central business district primarily comprises Duval Street, and includes much of the northwest corner of the island along Whitehead, Simonton, Front, Greene, Caroline, and Eaton Streets and Truman Avenue.The official city motto is “One Human Family.”