The London-based digital marketing agency is understood to have beaten four other companies for the business, which was previously handled in-house.
The move comes as Responsibletravel.com attempts to ramp up its online presence with a dedicated campaign of keyword bidding.
Nick Jones of I Spy said “We are delighted to be working with such a prestigious and intriguing brand.
“Responsible tourism is a growth area and we look forward to helping Responsibletravel.com reach more consumers through paid search.”
Responsibletravel.com was created in April 2001 and sells holidays from nearly 300 specialist operators and over 500 places to stay around the world.