First patrol: April–June 1942

After shakedown off the California coast, Silversides set course for Hawaii, arriving at Pearl Harbor on 4 April 1942. Departing Pearl Harbor on 30 April, Silversides headed for the Japanese home islands, in the area of Kii Suido, for the first of her many successful war patrols. On 10 May, just after 8:00 local time, the submarine used her 3-inch (76 mm) gun to heavily damage the Japanese guard boat Ebisu Maru No.5.^[10] During this 75-minute action, an enemy machine-gun bullet killed one of her deck gunners, Torpedoman's Mate Third Class Mike Harbin of Oklahoma, the only man lost in action aboard Silversides during World War II. Harbin was buried at sea later that evening. On 13 May, Silversides fired torpedoes at an enemy submarine; although explosions were heard, a definite sinking could not be confirmed.

On 17 May, while maneuvering through an enemy fishing fleet and approaching her targets, Silversides' periscope became entangled in a fishnet marked by Japanese flags held aloft on bamboo poles. The sub continued her approach, fishnet and all, and fired three torpedoes at the first ship, a 4,000-ton cargo ship. Two hits tore the victim's stern open. While that ship was sinking, the second cargo ship was also hit, but its fate could not be determined. Patrol boats were closing in as the submarine, probably the only American submarine to make an attack while flying the Japanese flag, quickly left the vicinity. After damaging a freighter and tanker in the same area, Silversides terminated her first war patrol at Pearl Harbor on 21 June.

Second and third patrols: July–November 1942

Silversides's second war patrol was also conducted in the area of Kii Suido, from 15 July to 8 September. On 28 July, she sank a 4,000-ton transport, followed by the sinking of the passenger/cargo ship Nikkei Maru on 8 August. She scored damaging hits on a large tanker on the night of 14 August and, on 31 August, sank two enemy trawlers before returning to Pearl Harbor.

Her third war patrol, conducted in the Caroline Islands, did not result in any sinkings, although severe damage was done to a large cargo ship and there were two observed torpedo hits on a Japanese destroyer or light minelayer, which did an undetermined level of damage. She terminated her third patrol at Brisbane, Australia, on 25 November.

Photo of Japanese ship attacked and damaged by USS Silversides on 14 October 1942

Fourth patrol: December 1942 – January 1943

Silversides departed Brisbane on 17 December 1942 and set course for New Ireland for her fourth war patrol. While far out at sea on the night of 22 December, the submarine's medical orderly, Pharmacist’s Mate First Class Thomas Moore, performed a successful emergency appendectomy on Fireman Second Class George Platter, using ether as anesthesia and rudimentary tools primarily fashioned from kitchen utensils. With the operation over at 3:00 on 23 December, the submarine surfaced only to be immediately forced down by a Japanese destroyer and compelled to endure a severe depth charge attack. Thinking herself safe, Silversides surfaced only to find the destroyer still there. Additionally, a Japanese airplane had arrived on the scene and proceeded to drop three bombs on the submarine, severely damaging her bow planes and causing them to lock on full dive. Silversides managed to level off just short of crush depth and eventually evaded the enemy ship before surfacing to recharge her batteries and effect emergency repairs.

While off Truk on 18 January 1943, Silversides torpedoed and sank her largest target of the war, the 10,022 ton oil tanker Toei Maru. Two days later, the submarine had one of her most productive days of the war. After paralleling a convoy throughout the daylight hours, she moved on ahead at sundown and lay in wait (an end around position). As the targets moved into range, Silversides fired torpedoes at overlapping targets and sank three enemy ships—the cargo ships Surabaya Maru, Somedono Maru, and Meiu Maru.^[11] The attack had scarcely abated when it was discovered that an armed torpedo was stuck in a forward torpedo tube. Since it was impossible to disarm the torpedo, the commanding officer decided to attempt to refire it, an extremely dangerous maneuver. The submarine moved in reverse at top speed and fired. The torpedo shot safely from the tube, disappearing as it moved toward the horizon.

When a serious oil leak was discovered later that night, the submarine left the patrol area two days ahead of schedule and returned to Pearl Harbor on 31 January for a major overhaul.

Fifth and sixth patrols: May–September 1943

Silversides's fifth war patrol commenced on 17 May and was conducted in the Solomon Islands area. Enroute the patrol area on 28 May, one of the more unusual moments of the war occurred. Stated in the 5th war patrol report as follows:

Proceeded on surface toward assigned position. On the 28th a frigate bird made a high level bombing attack, scoring a direct hit on the bare head and beard of the OOD, Lt. Bienia. No indication by radar prior to attack.^[12]

Continuing on, the submarine's primary mission for this patrol was to lay a minefield in Steffan Strait, between New Hanover and New Ireland, but she did not neglect enemy shipping. On the night of 10 – 11 June, she sank the 5,256-ton cargo ship Hide Maru; for her efforts, Silversides was forced to endure a severe depth charging. She returned to Brisbane for refit on 16 July.

For her sixth war patrol, under newly assigned Lt. Commander John S. "Jack" Coye, Jr., from 21 July to 4 September, Silversides patrolled between the Solomons and the Carolines. Since she was plagued with malfunctioning torpedoes and a scarcity of targets, she returned to Brisbane empty-handed.

Seventh and eighth patrols: October 1943 – January 1944

Silversides set sail on 5 October for her seventh war patrol, in which she sank four enemy ships in waters ranging from the Solomon Islands to the coast of New Guinea. On 18 October, she torpedoed and sank the cargo ship Tairin Maru, and, on 24 October, made a series of daring attacks to send the cargo ships Tennan Maru and Kazan Maru and the passenger/cargo ship Johore Maru to the bottom. She returned to Pearl Harbor for refit on 8 November.

Silversides patrolled off the Palau Islands for her eighth war patrol, where, on 29 December 1943, she brought havoc to an enemy convoy of cargo ships, sinking Tenposan Maru, Shichisei Maru, and Ryuto Maru. She terminated her eighth patrol at Pearl Harbor on 15 January 1944.

Ninth and tenth patrols: February–June 1944

For her ninth war patrol, Silversides departed Pearl Harbor on 15 February and set course for waters west of the Marianas Islands. On 16 March, she sank the cargo ship Kofuku Maru. The remainder of the patrol was devoid of worthwhile targets, so the submarine returned to Fremantle on 8 April.

While on her tenth war patrol, again off the Marianas Islands, Silversides destroyed six enemy vessels for a total of over 14,000 tons. On 10 May, she torpedoed and sank the cargo ship Okinawa Maru, followed up with the passenger/cargo ship Mikage Maru; and then sent the converted gunboat Choan Maru Number Two beneath the waves. Ten days later, she added to her score when she sank another converted gunboat, the 998-ton Shosei Maru. On 29 May, the submarine torpedoed and sank the cargo ships Shoken Maru and Horaizan Maru; and then headed for Pearl Harbor, arriving on 11 June. Two days later, she got underway for Mare Island Navy Yard for overhaul, returning to Pearl Harbor on 12 September.

Eleventh and twelfth patrol: September 1944 – February 1945

Silversides cleared Pearl Harbor on 24 September for her eleventh war patrol, conducted off Kyūshū, Japan. Although this patrol was unproductive, she aided in the rescue of a stricken sister submarine. Salmon (SS-182) had been badly damaged in a severe depth charging and was forced to surface and try to escape while fighting enemy escorts in a gun battle, a task for which a submarine is badly outmatched. The gunfire flashes brought Silversides to the scene. She deliberately drew the attention of some of the escorts, then quickly dove to escape the gunfire. Soon, submarines Trigger (SS-237) and Sterlet (SS-392) joined in helping Silversides to guard Salmon, and in escorting the stricken submarine back to Saipan, arriving on 3 November. Silversides terminated her eleventh patrol at Midway Island on 23 November.

Silversides' twelfth war patrol commenced on 22 December 1944, and was spent in the East China Sea. Despite aggressive searching, she found few worthwhile targets. However, when an opportunity did come her way, Silversides took full advantage. On 25 January 1945, she torpedoed the 4,556-ton cargo ship Malay Maru. She returned to Midway Island on 12 February.

Thirteenth and fourteenth patrols: March–July 1945

During her thirteenth war patrol, Silversides was a member of a coordinated attack group with submarines Hackleback (SS-295) and Threadfin (SS-410), patrolling off Kyūshū. Although she again found few worthwhile targets, the submarine did manage to damage a large freighter and to sink a trawler before returning to Pearl Harbor on 29 April.

Silversides's fourteenth and final war patrol began with a departure from Pearl Harbor on 30 May. This patrol was spent on lifeguard station in support of airstrikes on Honshu, Japan. On 22 July, she rescued a downed fighter pilot from the light aircraft carrier Independence (CVL-22), and two days later recovered a downed United States Army Air Forces airman. She ended this patrol at Apra Harbor, Guam, on 30 July. The submarine was undergoing refit there when the hostilities with Japan ended on 15 August.