Centcom said the US struck a land-attack cruise missile and four anti-ship missiles that "were prepared to launch against ships in the Red Sea".
It described the strikes as "self defense against a Houthi land attack cruise missile".
It comes after the US and UK unleashed attacks against 36 Houthi targets in Yemen, a day after the US military hit Tehran-backed groups in Iraq and Syria in retaliation for a deadly attack on US troops in Jordan.
The White House also warned that the US intends to launch further strikes at Iran-backed groups in the Middle East.
"We intend to take additional strikes, and additional action, to continue to send a clear message that the United States will respond when our forces are attacked, when our people are killed," White House national security adviser Jake Sullivan told NBC on Sunday.
The strikes are the latest blows in a conflict that has spread into the Middle East since October 7, when the Iran-backed Palestinian militant group Hamas stormed Israel from the Gaza Strip, igniting war.
Tehran-backed groups declaring support for the Palestinians have entered the fray across the region. Hezbollah has fired at Israeli targets at the Lebanese-Israeli border, Iraqi militias have fired on US forces in Iraq and Syria, and the Houthis have fired on shipping in the Red Sea and at Israel itself.
Iran has so far avoided any direct role in the conflict, even as it backs those groups. The Pentagon has said it does not want war with Iran and does not believe Tehran wants war either.
Mr Sullivan declined to be drawn on whether the US might attack sites inside Iran, something the US military has been very careful to avoid.
Speaking to CBS, he said Friday's strikes were "the beginning, not the end, of our response, and there will be more steps - some seen, some perhaps unseen".
"I would not describe it as some open-ended military campaign," he said.
Saturday's strikes in Yemen hit buried weapons storage facilities, missile systems, launchers and other capabilities the Houthis have used to attack Red Sea shipping, the Pentagon said, adding it targeted 13 locations.
The Houthi military spokesperson Yahya Sarea said the strikes "will not pass without a response and consequences".
Another Houthi spokesperson, Mohammed Abdulsalam, indicated the group would not be deterred, saying Yemen's decision to support Gaza would not be affected by any attack.
Residents described being shaken by powerful blasts. The Houthis did not announce any casualties.
US Secretary of State Anthony Blinken will visit Saudi Arabia, Egypt, Qatar and Israel in the coming days on his fifth trip to the region since October, which will focus on advancing talks on the return of hostages taken from Israel by Hamas in exchange for a temporary ceasefire in Gaza.
He will also make a push on a US-brokered mega deal between Saudi Arabia and Israel to normalise ties, which hinges on bringing an end to other Gaza conflict and steps toward a future Palestinian state.
The Yemen strikes are running parallel to the unfolding US campaign of retaliation over the killing of three American soldiers in a drone strike by Iran-backed militants on an outpost in Jordan.
On Friday, the US carried out the first wave of that retaliation, striking in Iraq and Syria more than 85 targets linked to Iran's Islamic Revolutionary Guard Corps (IRGC) and militias it backs, reportedly killing nearly 40.
Iran's foreign ministry said the latest attacks on Yemen were "a flagrant violation of international law by the United States and Britain", warning the continuation of such attacks was a "worrying threat to international peace and security".
Major shipping lines have largely abandoned Red Sea shipping lanes for longer routes around Africa. This has increased costs, feeding worries about global inflation while denying Egypt crucial foreign revenue from use of the Suez Canal.