Their invasion comes as President Bashar Assad tried to strengthen his grip on a strategic strip of land running from the capital to the Mediterranean coast.
With the regime scoring gains on the battlefield, the US and Russia could face an even tougher task persuading Assad and his opponents to attend talks on ending Syria's 26-month-old conflict.
Washington and Moscow hope to start talks with an international conference as early as next month, though no date has been set.
Government forces launched the offensive on the town of Qusair just hours after Assad said in a newspaper interview that he'll stay in his job until elections – effectively rejecting an opposition demand that any talks on a political transition lead to his ouster.
Even though the regime and the main opposition group have not yet committed to attending the conference, UN secretary general Ban Ki-moon said on Sunday that he is hopeful it can take place "very soon", possibly in early June.
In addition to the US and Russia, he said he has spoken with Britain, France, China and other key parties.
Previous diplomatic initiatives have failed, in part because of divisions within the international community and because the regime and the armed opposition believed they could achieve more on the battlefield than in talks.
Russia and the US have backed opposite sides in Syria.
Rebel control
Still, neither regime forces nor rebel fighters have been able to create significant momentum since the uprising against Assad erupted in March 2011 and last year escalated into a full-fledged civil war.
The rebels control large rural areas in the north and east of the country, while Assad has successfully defended his hold on the capital, Damascus, the coastal area and parts of Aleppo, Syria's largest city.
Before Sunday's offensive, Qusair had been ringed by regime troops and fighters from the Lebanese militia Hezbollah, an Assad ally, for several weeks.
Qusair lies along a land corridor between Damascus and the Mediterranean coast, the heartland of Assad's Alawite sect, an offshoot of Shiite Islam.
Many rebel fighters are Sunni Muslims and Qusair, overwhelmingly Sunni, had served as a conduit for shipments of weapons and supplies smuggled from Lebanon to the rebels.
Hadi Abdullah, a Qusair activist reached by Skype, said regime troops and Hezbollah fighters began shelling the town late on Saturday, followed by airstrikes early on Sunday that sent residents taking cover in basements.
The Britain-based Syrian Observatory for Human Rights, an activist group, said warplanes resumed bombing raids later on Sunday.
By Sunday afternoon, regime forces had advanced into the town, engaging in house-to-house battles with rebel fighters, Abdullah said.
Arrested rebels
Syrian state media said Assad's troops took control of the main square, the area around the municipal building, a sports stadium and a local church.
Syrian state TV said troops arrested rebel fighters who tried to flee Qusair dressed as civilians.
A government official said the regime left an escape road open to civilians, a claim denied by Abdullah, who said thousands of noncombatants were trapped in Qusair.
"We tried to get civilians out four times. They are not allowing us," he said of regime forces.
The Observatory said 52 people were killed in Qusair, including 48 fighters, three women and a male civilian.
Abdullah said the air raids destroyed at least 17 houses.
A field hospital was damaged last week, leaving the town with only one medical centre which was unable to handle the influx of some 400 wounded on Sunday, he said.
Civilian lives
The main political opposition group, the Syrian National Coalition, said some 40 000 civilians are currently in Qusair and expressed concern for their safety.
It urged the international community to step in to protect the lives of the civilians and called on the UN Security Council to denounce Hezbollah's involvement in the attack.
Six mortar rounds, apparently fired from Qusair, struck in nearby Lebanon, causing damage to a carpentry shop where a fire broke out, Lebanese security officials said.
There were no reports of casualties.
In the northern Lebanese port city of Tripoli, clashes erupted between residents of a predominantly Alawite area and a majority Sunni neighbourhood, Lebanon's National News Agency reported.
It said at least five people were wounded in the fighting. Events in Syria often raise tension among rival sects in neighbouring Lebanon, particularly in Tripoli.
The Qusair offensive was just the latest indicator that the joint US-Russian diplomatic initiative faces challenges.
Russia, despite its stated commitment to Syria peace talks, has reportedly delivered an advanced version of its Yakhont anti-ship cruise missiles to Syria, prompting US complaints last week about an "ill-timed" step.
Russia is a key political ally and arms supplier of the Assad regime, along with Iran.
US concerns
The Obama administration, meanwhile, wants to avoid getting drawn into the Syria quagmire, despite pressure to find a way to end the bloodletting that has left more than 70 000 dead.
US concerns have been heightened by the growing dominance of Islamic militants among the fighters, including those linked to the al-Qaeda terror network.
"For the US, [the conference] is mostly about postponing the tough decision-making Obama has been loath to get himself involved in, because he fears Syria will suck him in," said Peter Harling, a Syria expert at the International Crisis Group think tank.
In a further complication, Israel could get drawn in.
Israel's Prime Minister Benjamin Netanyahu warned on Sunday that he is ready to act if Syria attempts to ship advanced Iranian weapons to Hezbollah, saying that "we are prepared for every scenario".
Earlier this month, Israel struck twice near Damascus, to intercept purported shipments to Hezbollah.
Albert Aji in Damascus, Aron Heller in Jerusalem and Yasmine Saker in Beirut contributed reporting. – Sapa-AP