The Martin Agency will be responsible for Expedia.com's advertising including broadcast, print, radio, and digital brand marketing.
Media planning and buying and PR were not included in the scope of this review.
The Richmond Virginia-based agency won the account after a five-month review process handled by search consultants Ark Advisors.
More than 100 advertising agencies bid for the account before a shortlist was drawn up.
Paul Leonard, vice president-brand marketing of expedia.com, said: "We chose from a field of exceptionally talented and capable agencies.
"The Martin Agency is the best fit for Expedia.com based on the breadth and depth of their creative capabilities, strong cultural fit, and focus on delivering business results."
John B Adams, chairman and CEO of The Martin Agency, said: "More people book travel with Expedia.com than with any other online site.
"There are many compelling reasons why they're the category leader. We can't wait to work with their energetic team to reinforce their competitive advantages in the marketplace, serve their loyal customers and attract new ones."