Whitewater, which won the account after a three-way pitch, replaces incumbent Partners Andrews Aldridge.
The agency's task is to reinvigorate Save the Children's donor acquisition programme with a range of new creative and media tests.
The campaigns, which launch in November, will feature inserts, direct mail and door drops.
Jenny Morris, Save the Children's supporter acquisition manager, said: "Whitewater's creative work was incredibly powerful, and we were impressed with their thorough approach to the brief. We're very excited to be taking their ideas forward into live testing."
Niamh Neville, account director at Whitewater, said: "Save the Children is a great brand to work on. We were inspired by the brief, so we're thrilled to have won this pitch. We have high hopes for the autumn tests."