Barnsley will visit MK Dons in the fifth round of the FA Cup on the weekend that begins with Friday, February 15.
The Reds, who beat Burnley in the third round and Hull in the fourth round, are in the last 16 for the first time since they reached the semi-finals in 2008.
MK Dons are eighth in League One. They beat Barnsley's local rivals Sheffield Wednesday in the third round then won 4-2 at Premier League Queens Park Rangers in the last 32.
The teams have met five times since MK Dons were formed following the demise of Wimbledon. Barnsley were the Dons' first ever opponents in 2004 and the Reds have drawn three and won one of the sides' four league matches. Milton Keynes beat Barnsley in the League Cup in 2006.
MK Dons have former Barnsley player Anthony Kay in their squad.