"The trick called 'Deal of the Century', which is being pushed by an oppressive America and its traitorous companions, is a crime against human society, and not just the Palestinian people," state television quoted Khamenei as saying in a message to Muslim pilgrims performing the annual haj in Saudi Arabia.
"We call upon everyone to take an active part in defeating this deceit by the enemy," Khamenei said.
The message was read at a rally held by Iranian pilgrims, state television reported.
Saudi officials have asked Muslims to focus on rituals of worship and warned against politicizing the rite amid regional wars and heightened tension between Sunni Muslim Saudi Arabia and Shi’ite Muslim Iran.
The White House has yet to unveil US President Donald Trump's full Middle East peace plan that aims to end the conflict between Israel and the Palestinians and is led by Trump's advisor and son-in-law Jared Kushner.
Unlike his predecessors, Trump has not endorsed the Palestinian demand for statehood or the long-standing "two-state-solution" envisioned in previous negotiations that saw the goal as Israel and Palestine existing side by side in peace.
Kushner has so far presented a $50-billion economic revival plan for the Palestinian territories, Jordan, Egypt and Lebanon that is dependent on Israel and the Palestinians reaching a political settlement to their decades-old conflict.
The Palestinian leadership has broken off diplomatic ties with the White House, accusing Trump's administration of bias toward Israel. Washington has not said when it will present the full peace plan.