China, the host country, called for a "calm and patient attitude" for the meetings, put together after months of intense diplomacy. Envoys for the United States and North Korea shook hands, as did others, before they crisply got down to business.
South Korea, Russia and Japan are also participating.
All six have a stake in the outcome — even beyond wanting to keep the isolated communist North from becoming a nuclear threat.
South Korea wants to clear an obstruction from its policy of reconciliation with Pyongyang, Japan seeks progress on the issue of Japanese citizens kidnapped by the North during the Cold War. China hopes to avoid being dragged into a conflict between North Korea, a longtime ally, and the United States, a vital trading partner.
North Korea, faced with economic collapse, wants security guarantees and more food and humanitarian aid.
U.S. officials say they believe North Korea has one or two nuclear weapons, and experts believe it could produce five to six more within months. North Korea has withdrawn from key international agreements in recent months, including the Nuclear Nonproliferation Treaty.
In October, according to the United States, North Korea acknowledged a secret nuclear program, beginning the standoff and war of words that led to this week's talks. U.S. George W. Bush already was wary of North Korea, calling it in a January 2002 speech part of an "axis of evil."
Pyongyang insists Washington must change its "hostile policy" for the talks to produce any results. Otherwise, it said last week, "We will never give up nuclear deterrent force and settle accounts with the aggressors."
A spokeswoman for Bush said Washington welcomed the multinational talks.
"The president has always believed that this is a multilateral problem that requires a multilateral solution. And so we go into these discussions with great seriousness of purpose," the spokeswoman, Claire Buchan, said Tuesday.
Participating nations held smaller meetings behind closed doors in Beijing on Tuesday ahead of the formal talks. After conferring with Japanese and U.S. diplomats, Deputy South Korean Foreign Minister Lee Soo-hyuck said the preliminary discussions were "very useful."
At a dinner Tuesday night, delegates from all six nations mingled and "the atmosphere was friendly," said a Japanese Foreign Ministry official who spoke on condition of anonymity.
Elsewhere in Beijing, Assistant U.S. Secretary of State James Kelly met with Russian Deputy Foreign Minister Alexander Losyukov, who told the ITAR-Tass news agency that the American delegation is ready for "serious talks, sees certain prospects and is ready to use them." Losyukov didn't elaborate.
"All delegations are unanimous on setting the following tasks for the current round: First, to understand each other's positions; second, to create a more or less favorable atmosphere for the talks; and, third, to draft measures on which a plan for step-by-step settlement could rest," Losyukov told the agency.
China, meanwhile, basked in the prestige of hosting the six-nation talks. Its government news agency, Xinhua, ran more than a dozen related stories — including one touting the construction of a "hexagon table ... covered with dark green velveteen" for the talks.
Vice Foreign Minister Wang Yi said stability on the Korean Peninsula was a paramount goal of China, North Korea's one-time communist mentor and its only major ally.
Wang said participating nations should "adopt a calm and patient attitude, respect each other, conduct consultations on an equal footing, seek common grounds, and reduce disputes."
"The talks demonstrate the political will to seek peaceful ways to resolve the nuclear issue through dialogue," Wang said, according to Xinhua.
China has said repeatedly that it advocates a nuclear-free Korean Peninsula. Of late, it has warned the United States not to be heavy-handed in its dealings with North Korea.
Some say the talks themselves are something of a victory.
"If the parties of the six-nation talks this time discuss and agree on a date for the next round of the talks, I can consider that a meaningful and fruitful result," said Baek Seung-joo, chief of the North Korea Research Team at the Korean Institute for Defense analysis.