Spurs are only just entering the competition due to their European commitments, but could be tested by a team two divisions below them.
Thomas Frank is expected to make wholesale changes for the clash, while Doncaster are likely to throw everything at the match in hopes of causing an upset.
Read on to see how both teams line-up at the Tottenham Hotspur Stadium.
Tottenham line-up
As expected, Spurs go into the game with plenty of changes.
Antonin Kinsky comes in as the goalkeeper, with Pedro Porro, Kevin Danso, Archie Gray and Djed Spence completing the backline.
The midfield is marshalled by Rodrigo Bentancur and Joao Palhinha, with Xavi Simons given the nod in the No.10 role.
Brennan Johnson plays on the right, with Wilson Odobert on the left.
Mathys Tel comes in as the striker.
Doncaster line-up
Doncaster have gone with a strong line-up as they look to pressure their formidable foes.
Ian Lawlor is in goal, behind a defence of Tom Nixon, Jack Senior, Jay McGrath and Sean Grehan.
Ben Close partners Owen Bailey in midfield. behind the more advanced Joe Sbarra.
Canola Ajayi is on the right, with Toyosi Olusajya his opposite partner.
Glenn Middleton will look to bully the Tottenham defence.