Karmarama has been appointed to handle the advertising for all three brands, worth between £10m and £13m. It won the account after seeing off competition from WCRS and Brooklyn Brothers.
Farm, the incumbent on the Lastminute.com ad account for the past two years, was not involved in the pitch.
Farm's summer campaign for the travel site featured lilos and beach balls flying through the air, with the strapline "unleash summer".
The first work from Karmarama is expected to break in early 2009.
Manning Gottlieb OMD, which replaced Smarter Communications as Lastminute.com's media agency last year, was not been affected by the review.
Earlier this month, Lastminute.com hired Match.com marketing director Abbie Cranage as its head of marketing to replace Fleur Studd.
Cranage joined the company on September 25 and reports to Julie Davidson, Lastminute.com's UK marketing director.
Lastminute.com was founded in 1998 by Martha Lane Fox and Brent Hoberman. It was acquired by Sabre Holdings, owner of the Travelocity and Holiday Autos brands, in July 2005.
Davidson said: "We are delighted to announce the appointment of Karmarama as our lead communications agency who will work with us to take Lastminute.com's campaigns to a new level.
"During the pitch process, Karmarama delivered a strong strategic vision and displayed innovative creative thinking and we are looking forward to working with them."