Arena’s appointment comes ahead of a summer advertising campaign later this month.
Flight Centre is one of the world’s largest independent travel retailers, and has more than 2,000 stores in the UK, Australia, South Africa, USA, Canada and New Zealand.
Siobhan McGarvey, head of Flight Centre marketing, said: "Arena’s integrated approach, as well as their passion for and experience in our sector, made them stand out to us as partners for our business.
"We are looking forward to working with them to make the strategies we are developing a reality, and ultimately grow Flight Centre and its brands even further."
Flight Centre will continue to handle PPC, SEO, affiliates and social in-house.