On her first war patrol (under the leadership of Commander Stephen Ambruster, Annapolis class of 1928),[8] she sortied from Pearl Harbor,[9] hunting Japanese ships west of the Philippines.

[10] There, en route to her new station in Fremantle submarine base, Western Australia, she had an encounter with enemy vessels; on 13 February 1944 east of the Verde Island Passage, the Robalo had come across a convoy of two large ships escorted by a minesweeper, which dropped 13 depth charges and fired twice at the submarine with a deck gun;[10] although USS Robalo is "credited" with damaging a large freighter, firing four torpedoes at 3,100 yards (2,800 m),[11] in fact the attack was unsuccessful and no enemy vessels were damaged or sunk.

[16] When Chester W. Nimitz, Jr.[17] in USS Haddo (SS-255), made contact on his SJ radar and reported "many large ships",[18] Christie scrambled to respond.

[21] On 24 April 1944 off Indochina,[22] she was bombed by a Japanese antisubmarine aircraft, suffering shattered and flooded periscopes and loss of radar, while taking a harrowing plunge to 350 feet (110 m) after her main induction valve was improperly closed[21] (a casualty frighteningly reminiscent of Squalus) in diving to escape.

[24] When she returned to Fremantle, Captain "Tex" McLean (commanding Subron 16)[27] and Admiral Christie both considered relieving Robalo's skipper for his own safety.

On 2 July, a contact report stated Robalo had sighted a Fusō-class battleship, with air cover and two destroyers for escort, just east of Borneo.

[30] From these sources, it was concluded Robalo was sunk on 26 July 1944, 2 nautical miles (3.7 km; 2.3 mi) off the western coast of Palawan Island from an explosion in the vicinity of her after battery, probably caused by an enemy mine.

Four men swam ashore[31] and made their way through the jungles to a small barrier northwest of the Puerto Princesa Prison Camp, where Japanese Military Police captured them and jailed them for guerrilla activities.