The deal between Iran and six major powers limited Iran's uranium enrichment activity to make it harder for Tehran to develop nuclear arms - an ambition Iran has long denied having - in return for the easing of US and other sanctions.
But former US President Donald Trump abandoned the deal in 2018, denouncing it as one-sided in Iran's favor, and reimposed sanctions that have crippled Iran's economy.
"Iran has fulfilled all its obligations under the deal, not the United States and the three European countries ... If they want Iran to return to its commitments, the United States must in practice ... lift all sanctions," state TV quoted Khamenei as saying in a meeting with Air Force commanders.
"Then, after verifying whether all sanctions have been lifted correctly, we will return to full compliance ... It is the irreversible and final decision and all Iranian officials have consensus over it."
In response to Trump's withdrawal, Tehran has breached the deal's key limits one after the other, building up its stockpile of low-enriched uranium, refining uranium to a higher level of purity and using advanced centrifuges for enrichment.
US President Joe Biden, who took office last month, has said that if Tehran returned to strict compliance with the pact, Washington would follow suit and use that as a springboard to a broader agreement that might restrict Iran's missile development and regional activities.Iran has repeatedly said it could quickly reverse those violations if US sanctions are removed but has ruled out any talks over the country's ballistic missile program and Tehran's influence in the Middle East, where Iran and Saudi Arabia have been involved in proxy wars for decades.