The US delegation, led by Vice President JD Vance and including President Donald Trump's special envoy Steve Witkoff and son-in-law Jared Kushner, landed in two US Air Force planes at an air base in Islamabad on Saturday morning.
The Iranian delegation, led by parliamentary Speaker Mohammad Baqer Qalibaf and Foreign Minister Abbas Araqchi, arrived on Friday.
These will be the highest-level US-Iran talks since the Islamic Revolution of 1979 and the first official face-to-face negotiations between the two sides since 2015, when they reached a deal on Iran's nuclear program.
Trump scrapped the nuclear deal in 2018 during his first term in office.
That same year, Iran's then-Supreme Leader Ayatollah Ali Khamenei, who was killed at the start of the war six weeks ago, banned further direct talks between US and Iranian officials.
In a post on X, Qalibaf said Washington had previously agreed to unblock Iranian assets and to a ceasefire in Lebanon, where Israeli attacks on Iran-backed Hezbollah militants have killed almost 2000 people since March.
He said talks would not start until those pledges were fulfilled.
Israel and the US have said the Lebanon campaign is not part of the Iran-US ceasefire. Tehran insists it is.
Qalibaf said separately Iran was ready to reach a deal if Washington offered what he called a genuine agreement and granted Iran its rights, Iranian state media reported.
The White House did not immediately comment on the Iranian demands, but Trump posted on social media the only reason the Iranians were alive was to negotiate a deal.
"The Iranians don't seem to realise they have no cards, other than a short term extortion of the World by using International Waterways. The only reason they are alive today is to negotiate!" he said.
Vance, speaking en route to Pakistan, said he expected a positive outcome but added: "If they're going to try to play us, then they're going to find the negotiating team is not that receptive."
Islamabad was under an unprecedented lockdown on Saturday with thousands of paramilitary personnel and army troops on the streets.
"We have deployed multi-layer security for this event, which is based on co-ordination, intelligence and constant monitoring for zero disruption and full control," Pakistan's junior interior minister, Talal Chaudhry, told Reuters.
Trump on Tuesday announced a two-week ceasefire in the war, which has halted US and Israeli air strikes on Iran.
But it has not ended Iran's blockade of the Strait of Hormuz, which has caused the biggest-ever disruption to global energy supplies, or calmed the parallel war between Israel and Iran-backed Hezbollah in Lebanon.
Israeli ambassador to the US Yechiel Leiter and his Lebanese counterpart Nada Hamadeh Moawad will hold talks in Washington on Tuesday, Israeli and Lebanese officials said, amid the conflicting accounts on what those talks would cover.
Israeli attacks continued across southern Lebanon on Friday.
One strike on a government building in the city of Nabatieh killed 13 members of Lebanon's state security forces, President Joseph Aoun said in a statement.
Hezbollah said in a statement on its Telegram channel that it fired rocket salvos at northern Israeli towns in response.
Hours after the ceasefire was announced, Israel launched the biggest attack of the war, killing more than 350 people in surprise strikes on heavily populated areas, Lebanese authorities said.
Tehran's agenda at the talks includes demands for major new concessions, including the end of sanctions that crippled its economy for years.
It also wants acknowledgement of its authority over the Strait of Hormuz, where it aims to collect transit fees and control access in what would amount to a huge shift in regional power.
Iran's ships were sailing through the strait unimpeded on Friday, while those of other countries remained hemmed inside.
