Joe Biden will nominate as his secretary of state Tony Blinken, a veteran adviser who called Brexit a "total mess" and compared Britain leaving the EU to a dog catching a car and being run over.
As the president-elect's administration took shape he also announced John Kerry, the Democrat presidential nominee in 2004, as his climate star.
Jake Sullivan, a former Rhodes Scholar at the University of Oxford, will be national security adviser.
Mr Blinken, 58, and Mr Sullivan, 43, previously worked as advisers to Mr Biden when he was vice president, and have been described as his "brain trust" on foreign policy.
It signaled the president-elect's intention to fill his cabinet with officials who served alongside him in Barack Obama's administration.
Mr Obama said: "You're seeing a team develop that I have great confidence in."
The former president called Mr Blinken "outstanding, smart, gracious, a skilled diplomat, well regarded around the world."
However, Mr Biden's choice of Mr Blinken as chief diplomat was also an indication of how starkly different his view of post-Brexit Britain may be to that of Donald Trump.
Mr Blinken is a fluent French speaker who spent some of his formative intellectual years living in Paris.
He offered his assessment of Brexit on a podcast, hosted by fellow Obama administration alumni, in March last year.
At the time, Theresa May was trying to force her Withdrawal Agreement through Parliament.
"This is not just the dog that caught the car," Mr Blinken said. "This is the dog that caught the car, and the car goes into reverse, and runs over the dog. And it's a total mess.
"It's awful tough to walk that line between interfering in someone else's politics, but also standing up for your own interests, and our interest clearly would have been keeping Britain in."
Mr Blinken went on to criticise the "generational aspect" of Brexit. He said: "You have so many young Brits who feel like they have had the rug pulled out from under them. And they feel their elders have done something to them that they will regret."
He also said maintaining the Good Friday Agreement would be "certainly a heck of a lot tougher" after Brexit.
Mr Blinken has been called a "diplomat's diplomat" who has a "mind meld " with Mr Biden, and has worked with him in some capacity for two decades. In his spare time he plays guitar, and is a big fan of The Beatles.
Over the last four years he has been a vocal critic of Mr Trump's "America First' foreign policy, arguing that "big problems" do not have "unilateral solutions".
He has vowed to re-engage the US in multilateral agreements, including the Paris climate accord, Iran nuclear deal, and the World Health Organization.
How the president's credibility -- or not -- relates to our national security. https://t.co/vindunHnl4
— Antony Blinken (@ABlinken) April 18, 2017
Mr Blinken has indicated much of his work would focus on corralling allies to stop China's spreading influence, but also working with China on global issues including climate change.
The president-elect promised diversity in his cabinet, and Michele Flournoy was in contention to become the first female US defence secretary.
Mr Biden announced Alejandro Mayorkas, 60, as his nominee to be the first Hispanic homeland security secretary.
He picked Linda Thomas-Greenfield, who is black, as US Ambassador to the United Nations, and Avril Haines as director of national intelligence. All those picked served in the Obama administration.
As Special Presidential Envoy for Climate, Mr Kerry will sit on the National Security Council.
It is the first time the NSC, which advises the president on national security and foreign policy, will include a dedicated climate official.
It was also reported on Monday that Mr Biden is expected to name Janet Yellen to lead the treasury department, according to the Wall Street Journal.
Mrs Yellen, the 74-year-old economist who previously served as head of America's central bank and as a top economics adviser to former President Bill Clinton, would be the first woman to hold the position in US history.