The US president says North Korea must abandon any ambitions to acquire nuclear weapons in the face of stiff opposition from other countries.
As usual, leaders dressed up for the official Apec photo
George W Bush told the Asia-Pacific summit in Chile that the message to Pyongyang was clear: "Get rid of your nuclear weapons programmes."
North Korea said it would beef up its deterrent defences, official media in Pyongyang reported on Sunday.
The Apec summit meeting is being held under tight security in Santiago.
On Friday, tens of thousands of people protested on the city streets against capitalism and the Iraq war.
At least 189 people were detained.
Police have been deployed in strength throughout Santiago to break up unofficial protests.
Trade liberalisation and counter-terrorism are high on the agenda of the first official summit involving the leaders of all 21 member states, which include Canada, China, Japan, Russia and the US.
American officials say Mr Bush is using the Apec summit to map a strategy to resume talks with Pyongyang over its nuclear ambitions.
He had separate meetings with the Chinese, Japanese, Russian and South Korean leaders before the summit opened.
They, together with the US and North Korea, represent the countries involved in the stalled six-party talks on Pyongyang's nuclear ambitions.
"Five Apec members are working to convince North Korea to abandon its pursuit of nuclear weapons," Mr Bush told the conference.
"I can report to you today, having visited with the other nations involved in that collaborative effort that the will is strong, that the effort is united, and the message is clear to Mr Kim Jong-il [North Korean leader]; get rid of your nuclear weapons programmes."
A day after Mr Bush's message, a commentary in Rodong Sinmun, the official paper of the ruling Workers' Party, said North Korea needed to bolster its defences "as long as the US persists in its attempt to stifle the DPRK [North Korea] with nuclear weapons".
It said the US has "worked out a nuclear war scenario against the DPRK in top secrecy and has regularly staged drills for dropping nuclear bombs".
North Korea failed to attend the latest round of six-party talks in September aimed at resolving the deadlock over its nuclear programme.
US negotiators have denied reports that some of the countries want more concessions for North Korea, beyond a proposal made in June to allow South Korea and Japan to supply it with aid.
Before his speech, the US leader also had words of warning for Iran, following reports it has accelerated production of uranium material that could be used to make nuclear weapons.
"It's very important for the Iranian government to hear that we are concerned about their desires and we're concerned about reports that show that prior to a certain international meeting, they're willing to speed up processing of materials that could lead to a nuclear weapon," Mr Bush was quoted as saying by the AFP news agency.
The Apec summit is the first big international gathering that Mr Bush has attended since his re-election.
Members of the bloc, set up in 1989 mainly to promote trade among Pacific Rim states, now account for more than half of global economic output and almost half of all international trade.
The BBC's Elliott Gotkine in Santiago says there are hopes that Apec could take steps towards creating a free trade area for the Asia-Pacific region.