"Today we are announcing an arrangement that we think has the capability of sticking, but it's dependent on people's choices," Kerry said Friday in Geneva, Switzerland, appearing alongside Russian Foreign Minister Sergey Lavrov.
Kerry said the pact calls for the Syrian government and the opposition to respect a nationwide ceasefire scheduled to take effect at sundown Monday.
The Syrian regime announced its support of the ceasefire deal Saturday, according to the state-run al-Ikhbariya TV.
"That should put an end to the barrel bombs, an end to the indiscriminate bombing of civilian neighborhoods," Kerry said.
In February, a cessation of hostilities negotiated between Kerry and Lavrov fell apart within weeks, and efforts to reach a political settlement in the war-torn country
have been on the verge of collapse.
Airstrikes in Idlib
Airstrikes still went on Saturday in the city of Idlib, with at least 24 people killed, according to the Syrian Observatory of Human Rights. The Syria Civil Defense, a volunteer search and rescue group, tweeted a dramatic image of airstrike victims in the city that's about 35 miles southwest of the besieged Aleppo
Kerry and Lavrov said Friday that once the cessation of hostilities holds for seven days, their countries would begin working on military coordination in an effort to target one-time al Qaeda affiliate Jabhat Fateh Al-Sham, previously known as al Nusra Front.
"Going after Nusra is not a concession to anybody; it is profoundly in the interest of the United States to target al Qaeda," Kerry said, saying the group was planning attacks both in and outside of Syria, including ones directed at the United States.
"If groups within the legitimate opposition want to retain their legitimacy, they need to distance themselves in every way possible from Nusra and Daesh," Kerry added, referring to ISIS.
Kerry said this cooperation would entail "some sharing of information" with Russia pertaining to the delineation of the various groups on the battlefield. After the seven-day cessation of hostilities and delivery of aid, "US and Russian experts will work together to defeat Daesh and Nusra," Kerry said.
Kerry also said the accord would allow for humanitarian access to parts of Syria such as Aleppo caught in the crossfire and provide for the creation of a demilitarized areas around that northern city.
The secretary reiterated several times the deal was dependent on the adherence of all parties, both regime and opposition.
Citing private sources for al-Ikhbariya TV, Assad's government said "all hostilities in Aleppo will be halted for humanitarian reasons" and that one of the purposes of the deal is to find political solutions to the conflict.
It said a US-Russian coordination center will be created to target ISIS and Jabhat Fateh al-Sham with warplanes and high-precision weaponry.
World leaders welcome deal
Syria's opposition favors the new deal "if it is going to be enforced," Bassma Kodmani, a member of the High Negotiations Committee, said in a statement Saturday.
"When the cessation of hostilities was installed in February, the opposition -- 100 groups -- respected it. It was violated by the regime," Kodmani said. "So a return to a cessation of hostilities has been our demand."
The United Nations also welcomed the deal, saying Saturday that it expected all parties to facilitate in the delivery of humanitarian aid to besieged areas.
Foreign ministers in Turkey, Germany and the UK all greeted Friday's announcement.
Months of effort
The landmark agreement comes after months of unsuccessful efforts to reach a ceasefire between Assad's government and moderate rebels that would expand humanitarian access for hundreds of thousands of Syrians, efforts met by public skepticism from both the White House and the Pentagon.
Officials involved in the negotiations had been less than optimistic about a possible agreement in the latest round of talks in Geneva, with one senior official traveling with Kerry saying, "We are going to try, but our patience is not infinite."
But during Friday's drawn-out press conference, a lighthearted moment occurred when the Russian minister orchestrated the delivery of pizzas and two bottles of Russian vodka to the reporters, saying, "The pizza was from the US delegation, the vodka was from the Russian delegation."
Greater cooperation between US, Russia
The new US-Russia strategy hinges on deeper cooperation between the US and Russian military against extremist groups operating in Syria, particularly ISIS and the former al Nusra. The two sides are also holding talks on coordinating more closely the air operations they are both conducting in Syria.
But the United States has resisted coming to an agreement due to Russian and Syrian regime actions against civilians in Aleppo.
The United States wants a nationwide ceasefire in Syria between the regime and the rebels to create the conditions for UN-led political talks to end the five-year civil war
. The US-backed moderate opposition has refused to resume the UN-led talks unless a cessation of hostilities take hold and the regime and Russia end the siege and bombing of Aleppo.
"The opposition tells us they want to reach a deal with the Russians if in fact it would stop some of the worst forms of violence against the Syrian people," a second senior administration official said.
Staffan de Mistura, the UN special envoy for Syria, appeared with Kerry and Lavrov after the announcement to signal the United Nations backed the new agreement.
Earlier Friday, he said an agreement would make a major difference in terms of the cessation of hostilities and have a big impact on the delivery of humanitarian aid.
Both President Barack Obama and Defense Secretary Ash Carter
have had tough words for Russia in recent days, dimming the prospect of a deal on a ceasefire and closer military cooperation. The United States and Russia are both ostensibly fighting ISIS in Syria, but Washington has charged that Russia has mostly focused on bombing groups opposing Assad, a close ally. The United States supports some of those opposition groups.
Obama has questioned whether a deal was possible given the "gaps of trust" between the two countries after meeting Monday in China with Russian President Vladimir Putin on the sidelines of the G20.
The decision to deepen cooperation with Moscow was already controversial, given the Obama administration's public criticism of Russia's role in Syria.
Democratic Rep. Adam Smith, the ranking member on the House Armed Services Committee, said Friday he didn't trust Russia on a deal such as this.
"I think it's good and I applaud Secretary Kerry because I think the effort needs to be made. The only way to stop the carnage in Syria is to get some sensible transition away from Assad, and the Russians are key to that," Smith told Wolf Blitzer on CNN's "The Situation Room."
"I think in the meantime if we can get humanitarian aid to some of these places that are suffering, I mean that's a win, but at the end of the day, Syria will not make a successful transition to a reasonable government until Assad agrees to leave."