Following a shakedown cruise off the United States East Coast and in the Caribbean Sea, Seadragon returned to New England and, on 23 May 1940, departed New London, Connecticut, for the Philippine Islands.

With Commander, Submarine Division 17 (ComSubDiv 17) embarked, she arrived at Cavite on 30 November and commenced training operations as a unit of the Asiatic Fleet.

Two days later, on 10 December, she and sister ship Sealion, moored together, were caught in an enemy air raid against Cavite.

Submarine Rescue Vessel Pigeon, however, disregarded the danger and moved in to tow Seadragon into the channel; she continued into Manila Bay under her own power.

Temporary repairs were accomplished by tender Canopus and Pigeon; and, on the night of 15 December, Seadragon embarked members of the Asiatic Fleet staff.

Escorted by destroyer Bulmer, Seadragon moved south, via Surigao and Makassar Straits to Soerabaja, where she disembarked her passengers; received further repairs, exclusive of a paint job; and prepared for her first war patrol.

On 30 December, the submarine departed the Dutch naval base and set a course for the South China Sea to intercept Japanese shipping off the coast of Indochina.

Three salvos of bombs dropped close aboard, but Seadragon went deep and again made her way eastward—this time to investigate the cause of the plane sightings.

Red lead undercoating showed from the waterline to the side plating, and, "in spots", on the bow planes and propeller guards.

Tamagawa Maru (a 6,441-ton transport[5]), the fourth ship in line, went down, depriving the Japanese occupation force of a number of the reinforcement troops and the equipment she carried.

Among them were seventeen members of the crew at CAST (cryptanalysts and traffic analysts), including the commanding officer, Lieutenant Rudolph Fabian.

[7] At 20:53 on 8 April, she moored alongside Pigeon, to which she transferred fuel; offloaded seven tons of food (of the thirty she had taken aboard just for the besieged defenders[8]); took on 23 passengers (including the last seventeen members of the crew at CAST, among them "Honest John" Leitweiler and Rufus Taylor, who as a Japanese language specialist was worth his weight in gold[9]); and, at 21:29, got underway to resume her patrol.

No explosions were heard, but her torpedoes were seen, and the enemy ships turned on Seadragon and delivered a "well executed depth charge attack."

On the evening of 3 October, Seadragon departed the South China Sea and, five days later, commenced patrolling the approaches to Balikpapan.

On 1 December, she closed the New Britain coast to intercept traffic to the Japanese beachhead at Buna, and, during the next ten days, conducted several unsuccessful approaches on enemy formations.

On 21 December, Seadragon sighted an enemy submarine near Cape St. George, made her approach, and launched three torpedoes at the target.

From Pearl Harbor, Seadragon continued on to the West Coast, where skipper "Pete" Ferrall was detached to the Bureau of Ships.

On 4 June, she departed Truk and moved eastward to reconnoiter Ponape, thence proceeded into the Marshall Islands to patrol the sealanes converging on Kwajalein.

Four days later, she cleared the area, and, on 21 June, she arrived at Midway Island, whence she returned to Pearl Harbor for repairs to her steering gear.

Of the 44 days, 31 were spent on station near Wake and in the Marshall Islands where increased enemy air activity again hindered hunting and limited Seadragon's score to five freighters damaged.

On her eighth war patrol, 24 September to 5 November, Seadragon again returned to the Marshall Islands and spent 31 days hunting in the sea lanes to Kwajalein.

Seadragon's ninth war patrol, 14 December 1943 to 5 February 1944, took her back to the Caroline Islands where she hunted enemy shipping on the Truk-Saipan route and damaged two, possibly three, cargomen.

On 16 April, she moved past O Shima, and, that night, commenced patrolling off the Bungo Strait and Kii Channel entrances to the Inland Sea.

The patrol boats moved toward Seadragon as Daiju Maru sank and, during the next two hours, delivered a 40 depth charge attack.

On 17 May, she caught an armed trawler in a surface attack; set it afire with four-inch gun salvos, then closed the target to take off the uniformed enemy crew.

On 9 October, she arrived off Batan Island, established contact with Shark and Blackfish, and took position in a scouting line in the pack's assigned area.

At 09:20, Seadragon sighted three enemy merchantmen in a loose column with a torpedo boat destroyer and an airplane as escorts.

The next day, Seadragon continued on to Pearl Harbor, and, after refit, returned to California to provide training services to naval air units.

In May, she was transferred back to the Atlantic Fleet and for the final months of the war, provided training services at Guantanamo Bay and Key West, Florida.

On 29 October 1946, she was again decommissioned and berthed as a unit of the Atlantic Reserve Fleet where she remained until stricken from the Naval Vessel Register on 30 April 1948.