Massadio Haidara (pictured) returned from injury for the Magpies and fellow first-teamers Jack Colback and Henri Saivet also played.
Gabriel Osho's own goal put the Magpies ahead and, after Josh Barrett levelled for Reading before the break, Osho was sent off for conceding a penalty.
Tom Heardman's spot-kick was saved by George Legg but substitute Luke Charman scored twice and Callum Robets found the net, all in the final 12 minutes, to secure victory.
Newcastle moved up to ninth with victory. Reading stayed third.
See: Newcastle report
Newcastle: 24 Nov v Fulham (A) PL2
Reading: 26 Nov v Stoke City (A) PL2
(Photos courtesy of Serena Taylor/NUFC)