It was only the Academy team's second defeat in the last 15 matches in PAL and FA Youth Cup action.
Reading hit the front in the first minute but the lads were 2-1 up by the 20th minute thanks to Grant Ward and an own goal.
However, the home side levelled at 2-2 from the penalty spot a minute before the break and boosted by that goal, scored after 50 and 66 minutes to put the game beyond reach.
"In patches, we played really well," reported coach Alex Inglethorpe.
"It was disappointing to go 1-0 down so early, we'd prepared well but that goal was of our own making.
"We were soon level after good pressure on the ball, Mason Bush won possession and his cross was swept home by Grant Ward.
"Mason was involved again as we went 2-1 up after 20 minutes. After good work down the left, he got into the box and shot across the goalkeeper who saved it, but Grant and Victor Zapata-Caicedo followed in for the rebound and that forced a defender into an own goal.
"Victor had a goal disallowed at 2-1 and we were on top at that stage but we gave away a soft penalty for 2-2 just before half-time.
"To be fair to Reading, that goal made all the difference. They came out in the second half, stifled us in possession and capitalised on a couple of mistakes to to go 4-2 up.
"We did well in the latter stages without really creating that golden chance that might have got us back into the game.
"It was disappointing to concede four goals again but we do play with an open team and take risks on the ball. That is the style we play and we sometimes have to take chances if the players are going to learn to play like that."
Spurs U18s: Granger, Ogilvie (Ball, 71), Modeste, Ekong, McQueen, Munns, Lameiras, Zapata-Caicedo, Akindayini (McEvoy, 39), Bush, Ward.