The prince, grandson of Queen Elizabeth II, spoke at the Foreign Office as Prime Minister David Cameron met with European chiefs in Brussels before a summit this week where he hopes to secure reforms before an in/out referendum on Britains membership expected this year.
"For centuries Britain has been an outward-looking nation," said the prince. "We have a long, proud tradition of seeking out allies and partners."
"Weve always sought to explore what is beyond the horizon, that sense of mission and curiosity is something I know continues to drive our economy... armed forces and diplomatic services.
"Our ability to unite in common action with other nations is essential, it is the bedrock of our security and prosperity," Reuters quoted.
A spokesman for his Kensington Palace office insisted of the speech: "This was not about Europe."
The royal family does not usually intervene in political issues due to its constitutional position but has been known to issue carefully worded pronouncements on sensitive issues.
Before the 2014 referendum on whether Scotland would remain part of the United Kingdom, the queen said people should "think very carefully" about their decision while chatting to members of the public.
It later emerged that her words were agreed by her private secretary and the head of Britains civil service.
Cameron held talks with European Parliament chief Martin Schulz on Tuesday to drum up support for his controversial reform agenda ahead of a crunch summit Thursday and Friday.