"This is a crime and genocide that can be prosecuted in international courts," Khamenei said about the air raids carried out by Saudi Arabia and its allies, Al Jazeera reported citing Reuters news agency.
Khameini's reaction over Saudi-led intervention against Houthi rebels in Yemen is considered as strongest criticism of the campaign so far by an Iranian leader.
Saudi Arabia has repeatedly accused Iran of arming and supporting Houthi fighters, who control Yemen's capital Sanaa and who were on the verge of capturing the southern port city of Aden, where President Abd-Rabbu Mansour Hadi was based, before the Saudi air strikes began in March.
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Referring to Saudi king's son, Mohammed bin Salman, the defence minister who is leading the air campaign in Yemen, Khameini also said that foreign affairs in Saudi Arabia is being controlled by few inexperienced young men.
The Iranian condemnation came as Houthi fighters and allied military units captured Ataq, the capital of oil-rich Shabwa province, despite 16 days of bombardment by the Saudi air force.
The UN Security Council is also expected to vote on a resolution effectively imposing an arms embargo on Houthi fighters on Friday.