McDonnell's first involvement with politics came when he joined the National Democrats and stood as the party candidate in the 1970 election in North Antrim and lost to Ian Paisley.

In the 2005 general election McDonnell generated one of the most sensational results in Northern Ireland when he won South Belfast, primarily due to a split in the unionist vote.

[5] In June 2013, the SDLP abstained during the vote on the Civil Service (Special Advisers) Bill[6] in Stormont, ensuring its passing.

This led to claims from Sinn Féin that the SDLP was endorsing a "hierarchy of victims"' agenda and abandoning the principles of the Good Friday Agreement.

[9] On 8 June 2017, McDonnell lost his South Belfast seat to Emma Little-Pengelly (DUP) in the 2017 general election, despite increasing his vote from 2015.