The US Congress has two months to review the deal, which is opposed by Republicans, who control both Houses.
The senators on the Foreign Relations Committee are likely to question Mr Kerry at length on the content of the deal with Iran.
Many Republicans say last week’s accord conceded too much to Tehran.
Opponents within Congress could reject the agreement – but President Obama could veto their decision.
Negotiations between Iran and six world powers – the US, UK, France, China, Russia and Germany – began in 2006. The powers suspected Iran of pursuing a clandestine nuclear weapons programme, something Iran strenuously denied.
Iran, which wants international sanctions lifted, has agreed to rein in its nuclear activity and accepted a mechanism for inspections by nuclear officials.
The sanctions cannot be lifted while Congress is discussing the deal – until 17 September at the earliest.
Thursday’s meeting, which starts at 10:00 EST (15:00 GMT), gives Mr Kerry – along with Energy Secretary Ernest Moniz and Treasury Secretary Jack Lew – the chance to make a case to lawmakers to pass the deal.
But the three cabinet officials are likely to encounter tough questioning.
Could US Congress torpedo the deal?
• Congress has 60 days to review the agreement
• During that time, President Obama cannot lift the sanctions Congress has imposed on Iran
• Congress can reject the deal, and keep the sanctions in place, but Mr Obama can veto that
• It would need a two-thirds majority to overturn the veto, which is unlikely
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“Iran is a terror-sponsoring anti-American regime,” said Tom Cotton, a Republican senator from Arkansas.
“This deal is going to give tens of billions of dollars – at a minimum – without doing anything to rein in their support for terror or their support for America’s enemies.”
Mr Cotton, along with Mike Pompeo, a Republican Congressman from Kansas, wrote to Mr Obama on Wednesday to express their concern over what they called “side deals” nuclear inspectors were discussing with Iran.
A State Department spokesman said there were no secret deals and that there were only “technical arrangements”.
Bob Corker, the Republican chairman of the committee, said he had a number of concerns – in particular the amount of what he called “leverage” Iran would receive – but that he had not yet decided how to vote.
A number of other Democrats have said they do not know how they will vote, including Ben Cardin, the committee’s most senior Democrat, who said he had “many areas of concern”.