The agency pitched for the account last month against other, undisclosed agencies. There was no incumbent on the business.
Arena will be responsible for overseeing an expanded online affiliate partner programme in the UK for Mrandmrssmith.com.
Mr & Mrs Smith, which was founded in 2003, offers information on more than 350 boutique hotels across the world, as well as a number of vacation rental properties in Europe, and Alpine ski chalets.
Celebrities including Stella McCartney, Raymond Blanc and Dita Von Teese have contributed hotel reviews to the Mr & Mrs Smith books and website.
Dan Clays, chief strategic development officer at Arena, said: "We are delighted to have been appointed by Tamara [Lohan – founder of Mr and Mrs Smith].
"We love the brand and the history of how the business has been built up, and are really looking forward to growing this success with further innovation online."