Pompeo says US will expel 'every last Iranian boot from Syria'
"It's time for old rivalries to end, for the sake of the greater good of the region," said Pompeo at a keynote address in Cairo.
America "will use diplomacy and work with our partners to expel every last Iranian boot" from Syria and bolster efforts "to bring peace and stability to the long-suffering Syrian people," he added.
Pompeo also warned there would be no US reconstruction aid for areas controlled by Syrian regime head Bashar al-Assad until Iran and its proxies had left.
Washington's top diplomat was in Egypt on the latest leg of a whistle-stop regional tour aimed at shoring up Washington's Middle East policy following President Donald Trump's shock decision to withdraw 2,000 US troops from Syria.
Pompeo stressed the pullout would go ahead, despite comments in recent weeks appearing to walk back Trump's decision, but that the US would remain engaged.
The "decision to withdraw our troops has been made. We will do that. We will withdraw our forces, our uniformed forces, from Syria and continue America's crushing campaign", Pompeo told reporters at a joint press conference with his Egyptian counterpart Sameh Shukry.
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He also met earlier with Egyptian President Abdel Fattah al-Sisi, after arriving in Cairo late Wednesday on his longest trip since taking office last year which has already taken him to Jordan, Baghdad and the Iraqi Kurdish regional capital Erbil.
Trump's erratic policies
In his address entitled "A Force for Good: America Reinvigorated in the Middle East" at the American University in Cairo, Pompeo also took aim at former president Barack Obama, without naming him.
Trump's predecessor had "grossly underestimated the tenacity and viciousness of radical Islamism", Pompeo said.
And parroting Obama's words in his landmark 2009 speech in Cairo, Pompeo vowed that now was really "a new beginning" in ties between the US and the Middle East.
Pompeo's tour is aimed at urging regional allies to continue to confront the "significant threats" posed by Iran and jihadists.
Even though Islamic State group jihadists have been largely eradicated from Iraq, after capturing a vast swathe of territory in 2014, some still control a few pockets in war-torn Syria.
"The speech will likely go down well within Trump's administration, but many in Egypt don't view Iran with the same sort of vehement fear as policymakers in Washington," said The New Arab's James Brownsell.
"With US foreign policy dictated by the president's Twitter account, this speech - especially with its pops at Obama - appeared aimed more at a domestic audience, specifically the cable TV news-addicted occupant of the Oval Office, than it was a serious attempt to reach out to the Arab world."
Pompeo will also visit Gulf countries including Bahrain, the United Arab Emirates, Qatar, Kuwait, Oman and Saudi Arabia.
As he arrived in Egypt, the State Department described the country as a "steadfast partner in the anti-terror fight, and a courageous voice in denouncing the radical Islamist ideology that fuels it".
But there are rising concerns that US policy is getting bogged down. A long-promised Trump plan for a peace deal between Israelis and Palestinians has so far failed to materialise.
And many of the Trump administration's decisions have stoked confusion and angered many regional allies.