The weekly flight, which will stop at Antigua, forms part of the airline’s 2009/10 winter schedule.
Steve Ridgway, Virgin Atlantic’s chief executive, said that the carrier is "delighted" to be flying to Puerto Rico.
"This colourful, diverse and culturally unique island is a welcome addition to our Caribbean programme," he commented.
"From the stunning beaches and tropical rainforests to the charming colonial city of San Juan, there is something for every holidaymaker."
Virgin Atlantic already operates flights to the Caribbean destinations of Barbados, Antigua, St Lucia, Grenada, Tobago, Havana and Jamaica.
Flights to Puerto Rico will operate until April 24th next year.
The airline, which flies to 30 destinations around the world, carried almost six million passengers last year.
It recently announced its intention to launch flights to Chilean capital Santiago from London Heathrow.