The base has historically served as the homeport to various conventionally powered aircraft carriers of the United States Atlantic Fleet, including Shangri-La (1960–1971), Franklin D. Roosevelt (1956–1977), Forrestal (1977–1993), Saratoga (1957–1994), and, most recently, John F. Kennedy (1995–2007).

However, both houses of Congress have passed legislation authorizing about US$75 million for dredging and upgrades at NAVSTA Mayport to accommodate a nuclear-powered aircraft carrier.

[6][7] On 29 January 2010, the Quadrennial Defense Review Report stated that a nuclear aircraft carrier would be homeported at NS Mayport.

The action will help protect the fleet against a potential terror attack, accident or natural disaster, because all east coast aircraft carriers are currently based at Naval Station Norfolk, Virginia, according to the report.

"[8] The decision was opposed by elected officials in Virginia,[9] who would lose 3,500 sailors and their dependents, $425 million in revenue each year, and most importantly, 6,000 support jobs.

[13][14] The Virginia congressional delegation fought the loss of even one of Naval Station Norfolk's aircraft carriers boost to their economy by citing other areas such as shipbuilding to spend the Navy's tight budget.

Currently Wichita, Billings, Indianapolis, St. Louis, Minneapolis-Saint Paul, Cooperstown, and Marinette are assigned to the squadron, with upcoming ships Nantucket, Beloit, and Cleveland expected to be added as they come into service.

Currently, the surface group (SURFGRU) consists of the destroyers Ramage, Carney, The Sullivans, Donald Cook, Lassen, Mason, Farragut, Jason Dunham, Thomas Hudner, Delbert D. Black, and John Basilone.

The United States Coast Guard took over the base and operated a small "Boot Camp" there for several years, but they vacated Mayport in late 1947 due to budget cuts.

As helicopter aviation evolved during the Cold War, Mayport became the East Coast home for the Light Airborne Multi-Purpose System (LAMPS) MK III squadrons.