Direct proof of use
Cruise-missile use in the 2025 Israel-Iran Conflict is directly documented in the U.S. Operation Midnight Hammer strike on Iranian nuclear infrastructure. In a Pentagon briefing, Gen. Dan Caine said Tomahawk missiles were the last weapons to strike Esfahan during the operation, and the Defense Department transcript identifies a guided-missile submarine among the U.S. assets involved.
Defense News reported that a U.S. Navy nuclear-powered submarine launched more than two dozen Tomahawk land-attack cruise missiles into Iran on June 21, 2025, striking targeted infrastructure sites in Isfahan. Secretary of the Navy John Phelan later told lawmakers that the platform was an Ohio-class guided-missile submarine.
Sources: DOD Operation Midnight Hammer Transcript, Defense News Ohio-Class Role in Iran Strikes
Timeline
The cruise-missile strike occurred during the June 21-22, 2025 Operation Midnight Hammer sequence. The Defense Department briefing placed the main strike window between 6:40 p.m. and 7:05 p.m. Eastern time on June 21, corresponding to early June 22 local time in Iran, and said the Tomahawks struck Esfahan at the end of the sequence.
CSIS summarized the same operation as a strike package that included seven B-2 bombers and more than two dozen Tomahawk cruise missiles. It assessed that Isfahan appears to have been attacked only with Tomahawk cruise missiles rather than GBU-57 bunker-buster bombs.
Sources: DOD Operation Midnight Hammer Transcript, CSIS Operation Midnight Hammer Analysis
Narrative
The documented cruise-missile role in this conflict was a U.S. long-range land-attack strike against Iranian nuclear-related infrastructure, not a confirmed Iranian cruise-missile salvo against Israel. The publicly cited evidence for this record identifies U.S. Tomahawk land-attack cruise missiles fired from a submarine against Isfahan during Operation Midnight Hammer.
The cruise missiles complemented the air component of the operation. U.S. officials described B-2 bombers dropping GBU-57 Massive Ordnance Penetrators against Fordow and Natanz, while Tomahawks struck surface infrastructure at Esfahan. In that sequence, cruise missiles provided a stand-off naval strike option against a fixed strategic target inside Iran.
Sources: DOD Operation Midnight Hammer Transcript, CSIS Operation Midnight Hammer Analysis, Defense News Ohio-Class Role in Iran Strikes