Most Caribbean cruises leave from Miami, Ft. Lauderdale, Port Canaveral, and/or Tampa. However, some sail from Galveston, Mobile, New Orleans, Charleston, Norfolk, New York, and Baltimore.

The vast majority of Caribbean cruises depart from Florida, which serves as the global "Cruise Capital." PortMiami is consistently the busiest cruise port in the world, followed closely by Port Canaveral (near Orlando) and Port Everglades in Fort Lauderdale. These three ports handle millions of passengers annually due to their proximity to the islands and their massive airport infrastructures. Beyond Florida, San Juan, Puerto Rico, is a major "Southern Caribbean" hub, allowing ships to start deeper in the Caribbean and visit more remote islands without long days at sea. In the Gulf Coast region, Galveston, Texas, and New Orleans, Louisiana, have seen massive growth, primarily serving "Western Caribbean" itineraries to Mexico and Central America. On the East Coast, New York City and New Jersey (Cape Liberty) offer year-round Caribbean departures, though these often require several days of transit through the Atlantic. Other minor but significant departure points include Tampa, Florida, and Bridgetown, Barbados, the latter being a popular "fly-cruise" hub for British and European travelers looking to explore the Lesser Antilles.