Here are some of the key moments in their turbulent relationship:
1980s: United States pumps weapons, money and foreign fighters into Afghanistan, with the help of Pakistan to support extremist fighters defeat Soviet Union troops in Afghanistan.
1990: The United States imposes sanctions on Pakistan over Islamabad's covert nuclear programme. With the Soviet Union routed in Afghanistan and the Cold War ending, Pakistan had lost its importance as a regional ally.
1998: The United States imposes sanctions on Pakistan and India over their nuclear tests.
1999: Washington imposes more sanctions on Pakistan after army chief Pervez Musharraf topples a democratically elected government in a military coup.
2001: After the Sept. 11 attacks on New York and Washington, the United States asks Musharraf to help track down al Qaeda and remove the Taliban from power. Pakistan turns on its former Taliban allies and arrests al Qaeda leaders.
Washington removes all sanctions against Pakistan in the wake of Pakistan's support for its war against al Qaeda and other Islamist militant groups in Afghanistan.
2004: George W. Bush's administration designates Pakistan a "major non-NATO ally", boosting Islamabad's diplomatic prestige and giving Pakistan greater access to US military technology.
2011: CIA contractor Raymond Davis kills two Pakistanis in the eastern city of Lahore in January 2011. Davis was acquitted of murder and allowed to leave Pakistan after a $2.3 million payment was made to the men's families. US troops kill Osama bin Laden on Pakistani soil in May 2011. The raid, kept secret from Pakistani authorities, was a humiliation for Pakistan's powerful military and again raised questions about whether it was harbouring militants.
NATO helicopters and fighter jets attack Pakistani military outposts by accident, killing 24 soldiers. Pakistani retaliated by blocking a NATO supply route through its territory to Afghanistan for more than seven months.
2016: US Congress blocks the sale of F-16 fighter jets to Pakistan. Military aid to Pakistan reduced.
2017: US President Donald Trump outlines a new South Asia policy. Trump accuses Pakistan of harbouring "agents of chaos" and providing safe havens to militant groups waging an insurgency against the US-backed government in Kabul.