The specialist contract publisher and media sales house will be in charge of the magazine's sales from the January issue.
Reader's Digest is one of the UK's highest-selling magazines, with an average circulation of 541,282 in the first six months of the year (ABC) and a readership of 1.64 million in the year to June 2009.
Trevor Pryer, managing director of Publicom, said he was "delighted" to handle sales for "one of the world's best-known media brands".
He added: "The classified advertising proposition of the magazine is compelling due to the particularly responsive nature of its readership and we look forward to making a positive contribution to the magazine's revenue."
Earlier this summer, Publicom picked up the contract for Ikea's Family Live magazine from Mongoose Media.