On 21 December 1943, she cleared harbor on her first war patrol, bound for the heavily traveled shipping lanes south and west of Truk.

She performed a reconnaissance of Eniwetok on 12 January, and the next day scored a torpedo hit on a large ship, only to receive a severe depth-charging from her target's escorts.

She sank the IJN minelayer Tsugaru off Morotai on 29 June 1944, and again endured a heavy depth charge barrage as a result of her attack.

She pulled into Mios Woendi on 27 September for additional fuel, and sailed on 1 October with Dace to patrol the South China Sea in coordination with the forthcoming invasion of Leyte.

Immediately, Darter flashed the contact report, one of the most important of the war, since the location of this Japanese task force had been unknown for some days.

With Dace, she tracked the damaged cruiser through the tortuous channels of Palawan Passage until just after midnight of 24–25 October when Darter grounded on Bombay Shoal 9°27′22″N 116°55′59″E / 9.456°N 116.933°E / 9.456; 116.933.

When the demolition charges planted in Darter failed to destroy her, Dace fired torpedoes which exploded on the reef due to the shallow water.

[10] In addition to the Navy Unit Commendation, Darter received four battle stars earned during her four war patrols, the last three of which were designated as "successful".