Nato secretary-general Jens Stoltenberg said the 30-nation military alliance aims to set aside the divisions of the Trump era and focus on the security challenges posed by Russia and China.
Mr Stoltenberg said that Nato leaders are meeting on Monday "at a pivotal moment for our alliance, and today we'll open a new chapter in our trans-Atlantic relationship".
His remarks in Brussels came before he chaired a first Nato summit involving US President Joe Biden.
Nato faced turmoil for four years under former president Donald Trump.
Many allies are hoping to secure Mr Biden's assurances that the United States will stand by them in times of conflict.
Mr Stoltenberg said the leaders also want to reaffirm Nato's "dual-track approach" to Russia involving military deterrence, like the deployment of alliance troops in the Baltic countries and Poland, and dialogue.
After a series of meetings in Brussels, including with EU leaders, Mr Biden heads to Geneva for talks with Russian President Vladimir Putin on Wednesday.
Mr Stoltenberg played down the level of tensions with China, but he says Nato should take a firmer approach toward Beijing.
He says that "we are not entering a new Cold War, and China is not our adversary, not our enemy.
"But we need to address together as an alliance the challenges that the rise of China poses to our security."
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