The visitors forged into a 3-0 lead just before the hour mark but we then threatened an unlikely comeback as substitute Anton Walkes pulled a goal back and we enjoyed our best spell of the match.
Unfortunately, that spark of a possible revival only lasted 10 minutes when Rowan Liburd scored his second of the match and Reading's fourth on 70 minutes.
Cameron Carter-Vickers and Milos Veljkovic returned to our starting line-up after international duty with Filip Lesniak at left-back, Luke Amos central and Shayon Harrison up front.
The Royals took the lead on eight minutes. Liburd sent Lisandro Semedo away down the right and Christian Maghoma's attempted clearance sliding across his six-yard line cannoned into goalkeeper Tom Glover and home.
We enjoyed decent spells of possession but struggled to find a way through in the final third.
Reading pressed high and space was limited for the likes of Veljkovic and Amos to find a target with Emmanuel Sonupe, Anthony Georgiou and Harrison all willing runners, looking to get in behind.
At the other end, Tariqe Fosu dipped a free-kick just wide, Veljkovic made an important block from Semedo and Liam Kelly drilled just wide from 25 yards.
Reading doubled their lead on 40 minutes when we failed to clear our lines and Andrija Novakovich clipped in a cross for Liburd to head home from close range.
We had our first effort of note on 41 minutes when Cy Goddard did well to maintain possession under pressure, Kyle Walker-Peters found Harrison who fired low at Stuart Moore from the edge of the box.
No doubt buoyed by their first half showing, Reading came out with real purpose after the break, dominated the first 15 minutes and added to their lead from the penalty spot on 58 minutes.
Semedo got away down the right and his cross found Fosu, who was clipped by Walker-Peters. Referee Ian Cooper pointed to the spot and Fosu made no mistake for 3-0.
The team was handed a lifeline by Walkes a minute later, though. Harrison cut in from the right and his shot was deflected into the path of the substitute, who finished clinically from 12 yards.
That sparked belief into the players and we enjoyed our best spell in the next 10 minutes. Harrison drew the save of the match from Moore, a tip over from point-blank range, Veljkovic headed just wide from the resulting corner and Kenny McEvoy, off the bench on 63 minutes, saw a curler deflected inches wide.
Unfortunately, any hopes of a comeback were ended on 70 minutes when a ball over the top landed at Liburd's feet and he lashed past Glover from 14 yards for 4-1.
We kept plugging away without further rewards in the final 20 minutes as half-chances came and went at both ends, Fosu driving straight at Glover and Walker-Peters just failing to pick out Sonupe after a dart down the right.
Spurs U21s: Glover; Walker-Peters, Carter-Vickers (c), Maghoma, Lesniak; Amos, Veljkovic (Edwards 78); Sonupe, Goddard (Walkes 57), Georgiou (McEvoy 63); Harrison. Substitute (not used): Voss (GK).
Reading U21s: Moore; Long, Hyam, Sweeney (c), Griffin; Fridjonsson, Kelly; Semedo (Husin 71), Novakovich, Fosu; Liburd (Rinomhota 78). Substitutes (not used): Jules, Owusu, Ward (GK).