They rode through the city on the Routemaster as part of a campaign to showcase British commercial and cultural successes.
The pair were also presented with “mini-me” dolls of themselves.
Mr Cameron, 46, joked that the 14ft-high bus narrowly missed the clutter of street signs and lights as they drove to a Manhattan meeting.
He said: “I was worried that we were either going to lose Prince Harry or the traffic lights.”
The pair met entrepreneurs and were given the £90 lookalike dolls by UK firm MakieLab.
Army captain Harry, 28, who notoriously stripped naked in Las Vegas last year, pretended to look aghast.
Maker Jo Roach said: “He was impressed we got his Army Air Corps cap right, but he thought it looked a bit French, so adjusted it on the side.”
Mr Cameron jokingly moaned his doll’s hair had been brushed forward.
Jo — who has had £100,000 of Government funding — told him: “We’re trying to modernise you.” The PM replied: “I’ll take that tip on board.”
Mr Cameron later revealed that Britain has clinched a deal with US drugs giant Pfizer to become a global test site for medicines. Newcastle Hospitals Trust will hold the first clinical trials.
Meanwhile, Harry was last night hailed as “Prince Harry of Harlem” after hitting a home run at a community sports project.
He took on New York Yankees star Mark Teixeira — and nearly hit him out of the park.
The baseball star said: “He knew what he was doing. He’s a natural.”
Jolita Brettler, nine, said: “We were like ‘Wow!’. Who thinks a prince is going to play baseball?”
Harry earlier visited seaside resort Mantoloking in New Jersey, where all 521 homes were destroyed or damaged by Hurricane Sandy last October — and Seaside Heights where TV’s Jersey Shore is filmed.