Located to the oceanside of Key Largo, near Rock Harbor.

Most Spanish charts, from the very earliest ones, show Cayo Melchor Rodriguez. Caio di Melchor Roiz. on the Vingloons map of Cuba. (1639) Romans' chart (1773) shows Key Rodriguez. DeBraham chart (1772) shows Fox Island. George Gauld. in his Observations on the Florida Kays ,Reef and Gulf (1796) states: Melchor Rodrigues, or Cayo Rodrigues, called by the wreckers Fox Island. Captain Benjamin Barton of Carolina and the Bahamas, called the Key "Kay Melchoir Rodrigo." The logbook of the U.S. Revenue Cutter Marion (1832) uses Key Rodrigues. Blunt's American Coast-Pilot (1842) uses Melchor Rodrigues F.H. Gerdes, in a report written during his survey of 1849 states that the name was pronounced "Kay Dregas". Rodriguez Key on a survey map drawn by Charles Smith in 1873.

A document in the Spanish Archive of the Indies in Seville reveals that in 1582, a Spanish ship named La Salvadora, captained by one Melchor Rodriguez, was lost in the general area of Rodriguez Key. Later, in 1604, Captain Melchor Rodriguez is revealed to have been sailing from Saint Augustine to the West Coast of Florida. It seems very likely that this key was named after this man.