US Navy patrol ships discovered the weapons aboard what the Navy described as a stateless fishing vessel in an operation that began on Monday in the northern reaches of the Arabian Sea off Oman and Pakistan.
Sailors boarded the vessel and found 1400 Kalashnikov-style rifles and 226,600 rounds of ammunition, as well five Yemeni crew members.
It's just the latest interdiction amid the grinding war in Yemen that pits Iran-backed Houthi rebels against a Saudi-led military coalition.
Western nations and UN experts repeatedly have accused Iran of smuggling illicit weapons and technology into Yemen over the years, fuelling the civil war and enabling the Houthis to fire missiles and drones into neighbouring Saudi Arabia.
Iran denies arming the Houthis despite evidence to the contrary.
In an unusually pointed move, the statement late Wednesday from the Navy's Bahrain-based 5th Fleet blamed Iran for sending the weapons, saying the boat was sailing along a route "historically used to traffic weapons unlawfully to the Houthis in Yemen."
"The direct or indirect supply, sale or transfer of weapons to the Houthis violates UN Security Council Resolutions and US sanctions," the statement added.
Iran's mission to the United Nations did not immediately respond to a request for comment on the interception.
US Navy patrol ships transferred the confiscated weapons to the guided-missile destroyer USS O'Kane before sinking the fishing vessel because of the "hazard" it posed to commercial shipping. It said the Yemeni crew would be repatriated.
American seizures of arms bound for Yemen's war, typically Kalashnikov rifles, machine guns and rocket-propelled grenade launchers, began in 2016 and have continued intermittently. Yemen is awash with small arms that have been smuggled into poorly controlled ports over years of conflict.
The Navy's 5th fleet said it has confiscated some 8700 illicit weapons so far this year across the 2.5 million-square-mile area it patrols, including the strategically important Red Sea and the Persian Gulf.
Yemen's war erupted in 2014, when the Houthis seized the capital of Sanaa and much of the country's north. Saudi Arabia, along with the United Arab Emirates and other countries, launched a bombing campaign months later to restore the internationally recognised government and oust the rebels.
The war has killed some 130,000 people and spawned the world's worst humanitarian disaster.