Reading's Under-23s had skipper Gabriel Osho sent off as they lost 4-1 to a Newcastle United side that had three first team regulars involved.
Defender Massadio Haidara returned from injury, as well as Magpies midfielders Jack Colback and Henri Saivet taking part in their second string.
This result unfortunately ended the Royals' seven-match unbeaten run in the Premier League 2 that stretches back to September.
The scoring was opened after an unfortunate own goal from Royals' captain Osho, before Josh Barrett scored his sixth of the season to equalise for Reading, capitalising on a ricochet and slotting in.
Barrett almost turned the game around soon after, swerving a free-kick at goal but he was to be denied by the woodwork.
Having gone in level at the break, it was anyone's game as the teams stepped out for the second half.
Joel Rollinson could have put the Royals ahead just two minutes after the restart, being played clean through on goal but a fine save from Freddie Woodman stopped him.
However, Osho received his marching near the hour mark with a straight red card having been adjudged to have brought down Tom Heardman in the box.
George Legg rescued the Royals with a superb stop low to his left from the resulting spot-kick, with the Royals having a man disadvantage for the majority of the second half.
Scott Marshall's side were resolute in defence, though, holding the scores at one apiece until the Magpies finally broke their resistance in the 78th minute, with substitute Luke Charman heading in to restore the home side's advantage.
A curling effort from outside the area from Callum Roberts made sure of the result several minutes later, before Charman tapped in from close range in stoppage time to inflict the Royals' first Premier League 2 defeat in eight games.
Reading U23: Legg, Holmes, Osho, Andresson, Medford-Smith, East, Sheppard, Holsgrove (Davis 85), House (McIntyre 63), Barrett, Rollinson (Shokunbi 80).
Unused subs: Rosario, Howe.
Goals: Barrett 28
Yellow cards: Medford-Smith 58, House 59
Red card: Osho 57
Newcastle United U23: Woodman, Sterry, Haidara, Colback, Yarney, Gillesphey, Fernandez, Barlaser, Heardman (Charman 72), Saivet, Roberts.
Unused subs: Harker, Ward, Bailey, Kitchen.
Yellow cards: Yarney 35