Kerry struck his first of the season after just seven minutes with Orsi bagging his fourth of the season in this competition on the stroke of half-time.
The win maintained Town's 100% record in the competition and with results elsewhere in their favour secured progression to the knock-out stages with a game still to play.
Simon Weaver made a number of changes from the side that earned all three points at Oldham Athletic on Saturday. Into the line-up came Joe Cracknell, Nathan Sheron, Lloyd Kerry and Danilo Orsi, with Academy players Emmanuel Ilesanmi, Mason Wilson, Brad Williams and Ben Tweed starting the game on the bench.
Town grabbed the lead after seven minutes with the meaningful action of the evening. Gillespie's mistake in the visitors defence saw him robbed by Jack Muldoon and his backheeled pass teed up Kerry to crash home for the lead.
Weaver's side built on the momentum that the early goal gave them with Jack Diamond's probing runs down the left continually proving dangerous.
Diamond then found Thomson inside the box but his effort was blocked by Brad Cross.
Town's energy levels and high press was harassing their young opponents, not allowing them to settle for a moment. One such move saw Falkingham win possession inside the area but the skipper attempted the pass to
Orsi when the shot was surely the better option.
Town's right hand side was determined to offer as much as Diamond was down the left with the trio of Falkingham, Thomson and Ryan Fallowfield causing havoc amongst the Newcastle backline and a provide constant source of creativity in the first-half.
Niall Brookwell earned himself a yellow card on 35 minutes for a crunching challenge that felled Diamond.
Moments later the visitors registered their first attempt at goal when out of nowhere a driving effort aided by the wind from Elliot Anderson whistled just inches over the bar.
Savage then joined Brookwell in the book when he needlessly kicked the ball away.
Town got the reward their play deserved on the stroke of half-time when Muldoon weaved his way through the defence to release Orsi who coolly slotted home into the top corner.
The lead was almost extended five minutes after the break when Gillespie was forced to make a smart double save from Will Smith from a Town corner.
Anderson received a yellow card just before the hour mark after the Newcastle skipper went in late on Fallowfield, with Town's full-back also booked for his reaction.
Substitute Oliver then forced good work from Nathan Sheron, who recovered his position to deflect the effort behind for a corner. Despite the deficit the visitors were looking to be adventurous in possession when given the chance.
Diamond then tested Gillespie in the wet conditions with a fizzing effort that skidded off the turf before Brookwell was forced off through injury and replaced by Lucas De Bolle.
With a comfortable lead behind them though Town were able to take their foot off the gas without too much to their defence.
There was time for Ilesanmi to be handed his Town debut with five minutes remaining and he almost marked his entrance with a spectacular effort within seconds of coming on. He was then joined for the final minutes by both
Tweed and Williams, who also made their first appearances for the club.
TOWN: Cracknell. Fallowfield, Smith, Burrell, Thomson (Williams, 88), Falkingham (Tweed, 88), Kerry, Diamond, Muldoon (Ilesanmi, 84), Orsi.
Subs not used: Oxley, Hall, Wilson, Armstrong
Booked: Fallowfield (57), Sheron (70)
Goals: Kerry (7), Orsi (45)
Newcastle United u-21: Gillespie, Anderson, Brookwell (De Bolle, 80), Cross, Young, Oliver, Scott, Stephenson (Wilson, 78), White (Turner-Cooke), Savage, Wiggett.
Subs not used: Banda, Longelo-Mbule, Barrett, Flaherty.
Booked: Brookwell (35), Savage (39), Anderson (57)
Referee: Anthony Backhouse.