Pearl Lewis, 27, will take on the Labour left-winger in the 2015 general election.
She is an Aylesbury Vale District Councillor from Milton Keynes and works for the University of Buckingham.
Anti-third runway, she said: “The work starts now on an all-out campaign to win.
“I am especially against any airport expansion at Heathrow. I also look forward to working with our local businesses to support families back into work and keep our high streets thriving.”
Mr McDonnell, first elected in the 1997 Labour landslide , had a majority of almost 11,000 at the last general election.