They want to forge a common stance as they prepare to hand over security to Afghan forces by the end of 2014.
Some members have pledged aid to help Afghan forces tackle the Taliban insurgency on their own.
President Barack Obama warned of “hard days ahead”, and Afghan President Hamid Karzai said his country was fully aware of the responsibilities.
Barack Obama urged leaders to “pool resources”, and vowed to stand united to complete the Afghan withdrawal.
A number of NATO leaders have arrived from Washington, where they attended G8 talks that focused on the euro crisis.
The G8 group of leading industrial nations promised to promote growth alongside fiscal responsibility and insisted on the need for Greece to stay in the eurozone.
US President Barack Obama said there was an “emerging consensus” that European countries must now focus on jobs and growth.
The statements represented a shift away from Germany’s pro-austerity stance.
More than 50 leaders are attending the NATO meeting in Chicago.
Among them are heads of state and government from the 28 NATO countries, as well as Afghan President Hamid Karzai and his Pakistani counterpart Asif Ali Zardari.
As talks began President Obama spoke of a “transformational decade” in Afghanistan and the enormous sacrifices of the American people on the road to peace, stability and development.
The summit comes as several NATO leaders are under domestic pressure to withdraw troops from Afghanistan before 2014.
The new French President, Francois Hollande, has promised to pull out the country’s forces by the end of this year.
However, NATO Secretary General Anders Fogh Rasmussen said such moves were part of the plan.
“We are now in a process of gradually handing over lead responsibility for security to the Afghans and that process will be completed by the end of 2014 and during that process you will see withdrawal of troops, a shift from combat to support,” he said.
“It’s not a contradiction of our strategy, it’s a part of our strategy,” Anders Fogh Rasmussen added.
Some nations – including the US, Australia, Britain, and Germany – have made pledged to an international fund set to help Afghan forces after the NATO pullout.
The US is expected to pay half of an estimated $4 billion needed every year.
More than 10 years after the US toppled the Taliban regime, violence is continuing unabated in Afghanistan. According to UN figures, the number of deaths reached a record 3,031 in 2011 – the great majority caused by militants.
Earlier this month the Taliban announced the start of their annual spring offensive. On Saturday a suicide bomber killed at least 10 people, a number of them children, at a checkpoint in the eastern province of Khost.
The Obama administration is hoping that President Asif Ali Zardari of Pakistan will agree to reopen key NATO supply routes into Afghanistan, which were closed in November after US air strikes killed Pakistani troops.
Pakistan’s co-operation is regarded as key to the success of the international mission in Afghanistan, as 130,000 US-led troops fight a Taliban insurgency.
Also on the agenda at the NATO summit are plans for a US-led missile defense system for Europe, aimed at countering a possible threat from Iran.
The leaders are expected to announce the first phase of the scheme, with the deployment of US warships armed with interceptors in the Mediterranean and a radar system based in Turkey.
Russia has voiced strong opposition to the plan, saying it undermines the value of its nuclear deterrent.
The summit is taking place amid heavy security in Chicago.
Leaders from the Occupy movement have said they will join forces with anti-war demonstrators which have held protests ahead of the NATO meeting.
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