Biden, who arrived in London after attending an international conference in Munich, Germany, and Cameron discussed both foreign and economic policy concerns in a meeting that pool reports indicate lasted about 30 minutes longer than scheduled.
The leaders paused for a brief showing before the assembled media prior to speaking behind closed doors.
"We have a great relationship, and as you all know the most open relationship we have with any nation in the world is with Great Britain and we do have a lot to discuss," Biden said of Cameron and Deputy Prime Minister Nick.
The leaders said they planned to discuss the common challenges facing the two nations in Afghanistan, North Africa, Iran and the Middle East peace process. Also on tap was a new trade agreement between the United States and European Union they said could benefit both sides of the Atlantic.
Clegg, who was meeting Biden in person for the first time Tuesday, said the trade agreement would be a boon to both countries' economies.
"If we can work together to overcome the obstacles on both sides of the Atlantic, I'm absolutely sure -- we're all sure -- it'd be something that can create significant boosts to prosperity and jobs on both sides of the Atlantic."
Upon leaving, Biden did not take questions from the press.