The lads dominated in terms of possession but struggled to carve open the Stoke defence in game of few chances at Clayton Wood.
Stoke capitalised via a set-piece just after the hour and although we continue to push forward, home goalkeeper Dale Eve wasn't serious tested. In end, Stoke caught us on the break to secure victory in injury time.
Grant Ward went closest to breaking the deadlock in the first half. He won possession with Souleymane Coulibaly and let fly from the edge of the box, his effort cannoning back off the crossbar.
Our best spell of the half also saw Giancarlo Gallifuoco stride out of defende before firing over, Coulibaly head just over from Ruben Lameiras' free-kick and Milos Veljkovic's goalbound shot blocked by Edward Saunders.
At the other end, James Alabi's runs across our defensive line caught the eye but Stoke were restricted to one half-chance as Alex Grant headed over from Ryan O'Reilly's free-kick.
The second half followed the same pattern - we were in control of the ball, Stoke solid defensively - but the Potters struck the crucial opening goal on 62 minutes.
Charlie Ward clipped a free-kick into the danger area, the ball fell to Grant on the right angle and the centre-back managed to hook the ball back over Jon Miles and into the far corner.
Coulibaly glanced Kenny McEvoy's cross over soon after and our best chance arrived on 71 minutes when high pressing from substitute Roman Michael-Percil won possession, Coulibaly took over and shot low at goal - Saunders threw himself in to block.
We ended the match with three up front and with the game stretched, Stoke took advantage in the final seconds. Joel Taylor drove forward from half-way, cut onto his left foot and curled beyond Miles for 2-0.
Spurs U21s: Miles; A McQueen, Ball, Gallifuoco, Stewart; McEneff (Michael-Percil, 69), Veljkovic (Walkes, 85), Ward (D McQueen, 80); McEvoy, Coulibaly, Lameiras.
Stoke City: Eve; Wheeler, Grant, Saunders, O'Reilly (Taylor, 81); Rossi, Dawson (Monlouis, 69), Ward, Lecyane, Thomas; Alabi (Richards, 90+1). Unused sub: Westley, Gyollai.