The music festival will take place at Stewart Park and will also feature performances from Zara Larsson, Mabel and Khalid.
Making the announcement on the Radio 1 Breakfast Show, Greg James said: "I can't wait to take some of the best acts on the planet to Middlesbrough." The Big Weekend will be on 25 and 26 May.
Little Mix say they are "so excited" to perform at the event, now in its 16th year. It'll be the fourth time The 1975, who won two Brit Awards last week, have played Big Weekend but they said it's "great to be coming back, this time as headliners". More names will be added to the fantastic line up coming to Middlesbrough.