The review follows a number of senior management changes at the agency including the departure of its chief executive, Paul Hammersley, and its chief strategic officer, David Hackworthy, both of whom worked closely with the newspaper.
Andrew Fraser, the creative head on The Guardian's account, also left the agency to join FCB London as its creative director in February.
Although a shortlist has not yet been confirmed, it is expected that Hammersley and Hackworthy's new agency, The Red Brick Road, will be on the list. There is no intermediary handling the review and a decision is not expected until the summer.
The news is a blow to DDB, which is currently defending its Lurpak and Cravendale accounts. In addition, Mother is working on a brief for its PG Tips client, and Weetabix handed its £10m account to WCRS last month.
Last year, DDB created the campaign to relaunch the title in Berliner format as part of an £80m investment. The Guardian was named Newspaper of the Year at the British Press Awards this week.
The Guardian's circulation has risen by 4.4% year on year, according to the latest figures from the Audit Bureau of Circulations.
The decision does not affect Guardian Newspapers' relationships with either Mother or PHD.
If you have an opinion on this or any other issue raised on Brand Republic, join the debate in the Forum.