Andrew, 54, was hosting an event for start-up businesses, and seized the opportunity to photograph himself infront of the 350-strong audience.
"This is a unique day at the Palace because we are encouraging you to use your phones and electronic gadgetry," he announced. "As a result of that I've decided there's a bit of a thing going around about selfies."
The Prince then produced his phone and took the photo, which has since been shared 268 times.
He made a speech at the event, which called for the "most ambitious students" building fascinating technology and interested in starting up their own businesses.
Andrew tweeted from his account @TheDukeofYork throughout the event, signing off his tweets with his initials AY, confirming that he was running his own social media site rather than one of his team.
The Pitch @ Palace competition is aimed at young students interested in establishing their own companies and offers mentoring and cash from successful business leaders and investors.
"What we're lacking in this area in role models," Andrew said. "I want to give start-up businesses a boost."
Ellen DeGeneres kick-started a selfie craze when she shared her star-studded Oscars photo featuring the likes of Bradley Cooper, Brad Pitt, Angelina Jolie and Julia Roberts.
Since then a number of celebrities have jumped on the bandwagon, including former President Bill Clinton and his family who posed with chat show host Jimmy Kimmel.
Prince William famously starred in a selfie with a delighted schoolgirl over the Christmas holidays, and his dad Prince Charles also agreed to a photograph with teenager Joseph Wilson during a visit to Kent last month.