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For the ground pounders among us, a cruise missile submarine is a submarine that carries and launches cruise missiles (SLCMs and anti-ship missiles) as its primary armament. Missiles greatly enhance a vessel's ability to attack surface combatants and strike land targets, and although torpedoes are a more stealthy option, missiles give a much longer stand-off range, as well as the ability to engage multiple targets on different headings at the same time. Many cruise missile submarines retain the capability to deploy nuclear warheads on their missiles, but they are considered distinct from ballistic missile submarines due to the substantial differences between the two weapons systems' characteristics.

Originally early designs of cruise missile submarines had to surface to launch their missiles, while later designs could do so underwater via dedicated vertical launching system (VLS) tubes. Many modern attack submarines can launch cruise missiles (and dedicated anti-ship missiles) from their torpedo tubes while some designs also incorporate a small number of VLS canisters, giving some significant overlap between cruise missile submarines and traditional attack submarines. Nonetheless, vessels classified as attack submarines still use torpedoes as their main armament and have a more multi-role mission profile due to their greater speed and maneuverability, in contrast to cruise missile submarines which are typically larger slower boats focused on the long distance surface strike role.

The United States Navy's hull classification symbols for cruise missile submarines are SSG and SSGN – the SS denotes submarine, the G denotes guided missile, and the N denotes that the submarine is nuclear-powered.

The USN’s first SSG were developed in the early 1950s to carry the SSM-N-8 Regulus missile. The first of these was a converted World War II era Gato-class submarine, USS Tunny, which was fitted with a hangar capable of carrying a pair of Regulus missiles. Tunny was used as a test-bed for developing techniques of use for the missile system, before a second boat, USS Barbero was subsequently converted. From 1957, these two boats undertook the first nuclear deterrent patrols.

Subsequently, two larger diesel submarines of the Grayback-class were purpose built for the carriage of the Regulus missile, with each capable of accommodating up to four missiles, while a further boat, the nuclear-powered USS Halibut, could carry up to five missiles. Between September 1959 and July 1964, the five Regulus missile boats undertook deterrent patrols in the Pacific Ocean, in concert with the newly commissioned George Washington-class ballistic missile submarines (SSBN) in the Atlantic, until sufficient SSBNs were in service to replace them.

The SSM-N-8A, better known as the Regulus I was deployed from 1955 to 1964. It is a turbojet-powered second generation cruise missile with a 500nm range at a speed of Mach 0.85 with a circular error probable (CEP) of 0.5% at this range. and carrying a 3,000lb warhead such as the W5 (available with yields of 6/16/55/60/100 or 120kt) or W27 (1.5kt) nuclear warheads.

After being launched, the Regulus I would be guided toward its target by control stations, typically by submarines or surface ships equipped with guidance equipment. It could also be flown remotely by chase aircraft. Later, with improved navigational equipment, one submarine could guide it.

The first launch from a submarine occurred in July 1953 from the deck of USS Tunny, a World War II fleet boat modified to carry Regulus. Tunny and her sister boat USS Barbero were the United States' first nuclear deterrent patrol submarines. They were joined in 1958 by two purpose-built Regulus submarines, USS Grayback and USS Growler, and, later, by the nuclear-powered USS Halibut. Halibut, with its extremely large internal hangar could carry five missiles and was intended to be the prototype of a whole new class of cruise missile firing SSGN submarines.

The Navy strategy called for four Regulus missiles to be at sea at any given time. Thus, Barbero and Tunny, each of which carried two Regulus missiles, patrolled simultaneously. Growler and Grayback, with four missiles each, or Halibut, with five, could patrol alone. Operating from Pearl Harbor, Hawaii, the five Regulus submarines made 40 nuclear deterrent patrols in the Northern Pacific Ocean between October 1959 and July 1964, including during the Cuban Missile Crisis of 1962. According to the documentary "Regulus: The First Nuclear Missile Submarines" by Nick T. Spark, their primary task in the event of a nuclear exchange would be to eliminate the Soviet naval base at Petropavlovsk-Kamchatsky. These deterrent patrols represented the first ever in the history of the submarine Navy and preceded those made by the Polaris missile firing submarines.

The Regulus firing submarines were relieved by the George Washington-class submarines carrying the Polaris missile system. Barbero also earned the distinction of launching the only delivery of missile mail (yes they did pack mail for delivery to shore, just to prove they could.)

Additional submarines including USS Cusk and USS Carbonero were equipped with control systems that allowed them to take control of a Regulus in flight, thus extending its range in a tactical situation.

Regulus was also deployed by the U.S. Navy in 1955 in the Pacific onboard the cruiser USS Los Angeles. In 1956, three more followed: USS Macon, USS Toledo, and USS Helena. These four Baltimore-class cruisers each carried three Regulus missiles on operational patrols in the Western Pacific. Macon's last Regulus patrol was in 1958, Toledo's in 1959, Helena's in 1960, and Los Angeles's in 1961.

Ten aircraft carriers were configured to operate Regulus missiles (though only six ever launched one). USS Princeton did not deploy with the missile but conducted the first launch of a Regulus from a warship. USS Saratoga also did not deploy but was involved in two demonstration launches. USS Franklin D. Roosevelt and USS Lexington each conducted one test launch. USS Randolph deployed to the Mediterranean carrying three Regulus missiles. USS Hancock deployed once to the Western Pacific with four missiles in 1955. Lexington, Hancock, USS Shangri-La, and USS Ticonderoga were involved in the development of the Regulus Assault Mission (RAM) concept. RAM converted the Regulus cruise missiles into an unmanned aerial vehicle (UAV): Regulus missiles would be launched from cruisers or submarines, and once in flight, guided to their targets by carrier-based pilots with remote control equipment.

Despite being the U.S. Navy's first underwater nuclear capability, the Regulus missile system had significant operational drawbacks. In order to launch, the submarine had to surface and assemble the missile in whatever sea conditions it was in. Because it required active radar guidance, which only had a range of 225nm, the ship had to stay stationary on the surface to guide it to the target while effectively broadcasting its location. This guidance method was susceptible to jamming and since the missile was subsonic, the launch platform remained exposed and vulnerable to attack during its flight duration; destroying the ship would effectively disable the missile in flight.

Following the delivery of the 514th missile, Regulus I was phased out in January 1959. Many of the missiles were expended as targets or converted into target drones.