After shakedown training in waters off New London, Connecticut and Newport, Rhode Island, Amberjack got underway on 20 July, bound for the Pacific.

Three days later, she made contact with a large Japanese transport escorted by a destroyer, and fired a spread of four torpedoes at the vessels, but none hit.

Amberjack made her next contact with Japanese shipping on 25 September, spotting a large cruiser escorted by a destroyer.

On the morning of 27 November, the submarine encountered two enemy destroyers which were probably carrying supplies for Japanese forces on Guadalcanal.

On 29 November, while on patrol ten miles (16 km) east of the Treasury Islands, Amberjack spotted a surfaced Japanese submarine.

She again saw a Japanese submarine on 3 December proceeding toward the entrance to Shortland harbor and sent four torpedoes toward the fleeing enemy, but all failed to hit.

Within the space of one minute, six exploded close aboard, shook the vessel considerably, and caused numerous broken light bulbs forward.

She spotted another Japanese ship on 3 January 1943, a destroyer which apparently was waiting to rendezvous with a convoy from the Palau Islands.

She got underway on 24 January but was forced to return to Brisbane for repair of minor leaks which developed during a deep dive.

On 29 January she was directed to pass close to Tetipari Island and then proceed to the northwest and patrol the approaches to Shortland Basin.

At this time she was ordered to move south along the Buka-Shortland traffic lane and patrol east of Vella Lavella Island.

In a second radio transmission on 4 February, Amberjack reported having sunk a 5,000-ton freighter laden with explosives in a two-hour night surface attack that date in which five torpedoes were fired.

Chief Pharmacist's Mate Arthur C. Beeman, went to the bridge to assist the officer and was killed by machine gun fire.

All further messages to Amberjack remained unanswered, and when, by 10 March, she had failed to make her routine report estimating the time of her arrival at base, she was ordered to do so.

The enlisted men's recreation center at Submarine Base, Pearl Harbor, is named for Chief Pharmacist's Mate Arthur C. Beeman, who was killed in the gun battle of 4 February 1943.

Amberjack appears in the Harry Turtledove alternate history novel Days of Infamy, surfacing briefly during a deployment around Japanese-occupied Hawaii.