The pair were killed by police when they opened fire outside the conference in Garland, Texas, that was run by an extreme free-speech group.
A security guard was shot in the ankle, taken to hospital and later released. Nobody else was injured.
One of the two attackers was identified as Elton Simpson, 30, who was known to the FBI. Fifteen minutes before the attack, he sent a tweet reading: “May Allah accept us a Mujahideen.”
In the past, he has tweeted support for Islamic State (IS), the terrorist group that has taken control of large parts of Iraq and Syria.
The first annual Muhammad Art Exhibit and Contest was organised by the American Freedom Defense Initiative, which is classified as an anti-Islam hate group by the Southern Poverty Law Centre, an anti-discrimination watchdog.
Attendees were encouraged to draw depictions of the Prophet Muhammad for a $12,500 (£7,500) prize. Images of Muhammad are considered blasphemous in Islam.
The keynote speaker was right-wing Dutch politician Geert Wilders, who has been placed on an al-Qaeda hit list and was banned from entering the UK because of his views on Muslims.
According to US reports, organiser Pamela Geller compared the attack to that in Paris last year in which Islamic extremists stormed the offices of satirical magazine Charlie Hebdo and shot dead 12 people. Ms Geller said: “The Islamic jihadis are determined to suppress our freedom of speech violently. They struck in Paris and Copenhagen recently, and now in Texas.”
She added: “The First Amendment protects all speech, not just ideas that we like. Who would decide what’s good and forbidden? The Islamic State?”
The two men drove up to the event at the Curtis Culwell Centre at about 7pm on Sunday as it was drawing to a close and began firing as soon as they got out of their car.
Garland mayor Douglas Athas said the first suspect had been shot dead immediately. The second was wounded and reached for his backpack when he was shot again.
The suspects wore bulletproof vests and one was apparently wearing a New York Yankees cap on his head.
Witnesses described hearing a “boom, boom” noise and, as the 200 attendees were held inside by security, they joined hands and sang God Bless America.
Counter-terrorism analyst Daveed Gartenstein-Ross said jihadis in online forums were saying the attack had been simplistic and that the men had little weapons training.
But he said: “This wasn’t an attack that was carried out by some random Muslim. This was an IS supporter, he hated a variety of things, the worst of the worst in terms of ideas.”
Ms Geller has attracted controversy before for her comments in the wake of 9/11 and her opposition to a mosque that was due to be built near Ground Zero in New York.
Her organisation paid for anti-Islam adverts which were put on the New York City transit system and featured images of James Foley, a US journalist executed by IS.
FBI investigators were last night searching an apartment in Phoenix, Arizona, where Simpson lived. According to a criminal complaint filed in 2011, he has been known to the FBI since at least 2006 and was investigated for allegedly attempting to set up a terror cell in Arizona.