Russia's military claimed to have killed the jihadist during an airstrike in May, after targeting a meeting of top IS commanders in Raqqa, Syria.
Earlier this month, just days after the liberation of Mosul, the group's de facto capital in Iraq, a monitoring group said it had "confirmed information" al-Baghdadi was dead.
But US defence secretary General James Mattis said on Friday: "I think Baghdadi's alive... and I'll believe otherwise when we know we've killed him.
"We are going after him but we assume he is alive."
His belief was supported by America's counter-terror chief Nicholas Rasmussen.
"I've seen nothing that would lead me to believe that the leader of ISIS (Islamic State) has been removed from the battlefield," said the director of the US National Counter Terrorism Center.
"We know a good bit. We just don't have information that would confirm his death and demise."
The US army's General Raymond Thomas, the head of special operations, admitted the country's military has come "particularly close" to getting al-Baghdadi in the past but he had slipped away.
He blamed a media leak for ruining at least one promising lead.
The Russian claim, made in June, could not be confirmed by the US at the time, with America's military leading international efforts to defeat IS in Syria and Iraq.
The US again couldn't confirm the recent announcement by the UK-based Syrian Observatory for Human Rights it had verification of al-Baghdadi's death.
Having lost control of Mosul, where al-Baghdadi declared the so-called IS caliphate in 2014, the group are also under pressure in Raqqa, following the entrance of Western-backed forces into the city.
The US government are offering up to $25m (£19m) for information leading to al-Baghdadi's location, arrest, or conviction.
He is believed to have been born in Iraq, where he was detained by US-led coalition forces in 2004 but released after being viewed as not a high-level threat.