The appointment comes as it seeks to increase brand awareness and encourage more customers to buy their full travel package online rather than just flights.
Expedia wants customers to be lured into buying their accommodation and car hire, on which it enjoys higher margins than selling flights.
CHI scooped the account after pitching against Wieden & Kennedy, CDD Testa and incumbent agency Euro RSCG Wnek Gosper. Marketing director Beverly Shaw, who joined the company from Coca-Cola in November, oversaw the review.
Expedia this week embarked on what it claimed was its biggest ever January promotion, backed by a multi-million pound ad campaign. It purports to offer big discounts on holiday packages as well as a range of incentives.
Expedia launched in October 1998 with Microsoft as its main shareholder.
Microsoft sold its 65% majority stake last year to USA Interactive, the company that owns ticket retailer Ticketmaster.