Again departing Brisbane, Australia on 26 January 1943, USS Amberjack, under Lt.Cdr. John Archibald Bole, Jr., started her third war patrol in the Solomons area. 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. Orders were radioed on 1 February for her to move north and patrol the western approaches to Buka Passage. Having complied with these orders, Amberjack made her first miles southeast of Treasury Island on 1 February, and of sinking a two-masted schooner by gunfire twenty miles from Buka the afternoon of 3 February 1943. At this time she was ordered to move south along the Buka-Shortland traffic lane and patrol east of Vella Lavella Island.

Making 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. This is uncorfirmed by Japanese sources and the target remains unidentified.
On 8 February, Amberjack was ordered to move to the West Side of Ganongga Island and on the 10th, she was directed to keep south of Latitude 7-30'S, and to cover the traffic routes from Rabaul and Buka to Shortland Basin. On 13 February Amberjack was assigned the entire Rabaul- Buka-Shortland Sea area, and told to hunt for traffic.

The last radio transmission received from Amberjack was made on 14 February 1943. She related having been forced down the night before by two destroyers, and that she had recovered from the water and taken prisoner an enemy aviator on 13 February. She was ordered north of Latitude 6-30 ‘S, and told to keep hunting for Rabaul traffic.

All further messages to Amberjack remained unanswered, and when, by March 10, she had failed to make her routine report estimating the time of her arrival at base, she was ordered to do so. No reply was received, and she was reported as presumed lost on 22 March 1943.

Reports received from the enemy since the end of the war record an attack, which most likely sank Amberjack. On 16 February 1943, the Japanese torpedo boat Hiyodori (offsite link) and submarine chaser Ch-18 (offsite link) attacked a submarine with nine depth charges south of Rabaul in 05º05'S, 152º37'E. An escorting patrol plane had previously attacked the submarine. A large amount of heavy oil and parts of the hull came to the surface. This attack is believed to have sunk Amberjack. However, no final conclusions can be drawn, since USS Grampus (SS 207) was lost in roughly the same area and at about the same time. From the evidence available, particularly a life preserver inscribed with the words "Philadelphia Navy Yard" it is considered most likely that the attack of 16 February sank Amberjack, but if she did survive this attack, any one of the attacks and sightings thought to have been made on Grampus might have been made on Amberjack.