CAIRO - For more than 70 years, the United States (US) and Iran have been trapped in a cycle of hostility centered on regional security and Iran's nuclear ambitions, with tensions repeatedly boiling over into open confrontation.

The following timeline traces the key milestones in their fraught relationship:

-- 1953: US intelligence agencies orchestrated a coup that overthrew then-democratically-elected Iranian Prime Minister Mohammad Mosaddegh, reinstating the US-backed Shah Mohammad Reza Pahlavi.

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-- 1957: The United States and Iran signed a civil nuclear cooperation agreement as part of then US President Dwight Eisenhower's "Atoms for Peace" initiative, laying the foundation for Iran's nuclear ambitions.

-- 1972: Then US President Richard Nixon visited Iran and pledged to sell Teheran any US weapons except nuclear arms in exchange for Iran's role in safeguarding US interests in the Middle East.

-- 1979-1981: Iran's Islamic Revolution, led by Ayatollah Ruhollah Khomeini, toppled the Pahlavi dynasty and established the Islamic Republic of Iran. On Nov 4, 1979, Iranian students seized the US Embassy in Teheran, taking 52 Americans hostage. In response, then US President Jimmy Carter severed diplomatic ties and imposed sanctions on Iran.

-- 1980-1988: During the Iran-Iraq War, the United States backed Iraq, further straining relations with Teheran.

-- 1984: The United States designated Iran as a "state sponsor of terrorism" following a 1983 attack on a multinational barracks in Lebanon's Beirut that killed over 200 US service members. Washington attributes the attack to Iranian-linked militants.

-- 1988: A US warship shot down an Iranian civilian flight, killing over 200 people on board.

-- 1995: The administration of then US President Bill Clinton tightened sanctions, banning US trade with and investment in Iran.

-- 2002: Then US President George W Bush labeled Iran, Iraq and the Democratic People's Republic of Korea as an "axis of evil" in his State of the Union address.

-- July 2015: Iran reached a landmark nuclear agreement, formally known as the Joint Comprehensive Plan of Action (JCPOA), with the United States, Britain, France, Russia, China and Germany. Under the deal, Teheran agreed to curb its nuclear program in exchange for sanctions relief.

-- 2018: The administration of US President Donald Trump unilaterally withdrew from the JCPOA and reinstated "maximum pressure" sanctions, a move widely condemned by the international community.

-- 2019: The United States designated Iran's Islamic Revolutionary Guard Corps (IRGC) as a Foreign Terrorist Organization. Iran subsequently labeled the US Central Command and its forces in West Asia as a "terrorist group".

-- 2020: A US airstrike in the Iraqi capital Baghdad killed Qassem Soleimani, commander of the IRGC's Quds Force. Iran retaliated by launching missiles at military bases in Iraq housing US troops.

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-- 2025: Beginning in April, Iran and the United States held five rounds of indirect talks over the Iranian nuclear issue and US sanctions relief. On June 13, ahead of a planned sixth round, Israel launched large-scale airstrikes on Iran. On June 21, the United States initiated Operation "Midnight Hammer," with Trump announcing successful strikes on Iran's nuclear facilities at Fordow, Natanz and Isfahan. A ceasefire between Iran and Israel took effect on June 24.

-- Late 2025: Protests erupted across Iran over rising prices and currency depreciation, with unrest causing casualties among security personnel and civilians. Iran accused the United States and Israel of instigating the turmoil, while Washington threatened military intervention.

-- February 2026: The United States and Iran resumed indirect negotiations and conducted three rounds of talks, as Washington massed significant forces in the Middle East. On Feb 28, the United States and Israel launched a joint military strike against Iran, killing Iran's Supreme Leader Ayatollah Ali Khamenei. Iran immediately retaliated with missile and drone strikes against Israel and US military assets across the region.