The young Magpies trailed in the opening stages at the Jakemans Community Stadium followjn g Sam Osborne's curling long-range strike but found themselves ahead before the half-time break courtesy of Ben Parkinson's first-half brace.
Newcastle, however, conceded twice in the space of five second-half minutes as Pemi Aderoju's close-range finish levelled the Group C encounter before Frankie Maguire's bundled strike in the closing stages ultimately proved the difference in Lincolnshire.
Diarmuid O'Carroll made four changes from the side which claimed a 1-0 win against Crystal Palace in the Premier League 2 on Friday as Isaac Hayden, who made his senior international debut for Jamaica last month, was named in the starting XI along with Magpies skipper Cathal Heffernan, Alfie Harrison and Darren Palmer, replacing Travis Hernes, Matt Targett, Jay Turner-Cooke and Trevan Sanusi respectively.
Targeting a fifth successive win across all competitions, Newcastle fell behind in the sixth minute through Osborne's impressive strike as the Boston winger dispossessed Heffernan on the left flank before curling a speculative effort from distance into the top right-hand corner.
Magpies goalkeeper Aidan Harris produced a key save to prevent the National League outfit doubling their lead in quick succession as the 17-year-old shot-stopper, who signed his first professional contract withe his boyhood club last summer, blocked Pemi Aderoju's low drive inside the penalty area with his left foot.
In the 14th minute, Newcastle drew level as Parkinson netted his eighth goal of the 2024/25 campaign at second-string level. After a dangerous attacking move saw the ball fall into Alfie Harrison's path, the Keighley-born teenager's low drive took a kind deflection off the 19-year-old striker before the ball rolled into the bottom left-hand corner.
Parkinson, who made his Premier League debut for the Magpies away at AFC Bournemouth in November 2023, was unfortunate not to double his and the visitors' tally shortly after as Lewis Miley's teasing cross into the box was only half cleared by Tom Leak but the Boston defender was able to block Parkinson's drilled effort inside the box.
Lewis Miley, who made his England Under-21s debut last month, created an opportunity in front of goal as the Stanley-born midfielder collected Isaac Hayden's pass before his strike from the edge of the penalty area was held by Boston goalkeeper Aidan Stone.
Parkinson fired Newcastle's youngsters in emphatic fashion in the 43rd minute, controlling Palmer's cutback before slamming the ball into the roof of the net, his fourth goal in his last four matches at under-21 level.
Harris produced an outstanding save to prevent Keaton Ward equalising for the hosts on the stroke of half-time, tipping the Pilgrims midfielder's stinging free-kick over the crossbar.
Parkinson went close to completing his hat-trick in the second-half as the in-form forward advanced into the box but his resulting low effort was pushed around the post by Stone before Miley's free-kick from the edge of the box flew narrowly over the crossbar.
Newcastle found themselves on level terms in the 76th minute as Aderoju equalised for the hosts, with the Boston striker on hand inside the six-yard area to fire the ball home from Maguire's low cross.
United's second-string were delivered a further blow in the 81st minute as Maguire turned from provider from goalscorer, scrambling the ball home at the back post following an inviting cross into the box from the right flank.
Heffernan was unfortunate not to take the game to a penalty shoot-out in stoppage-time, gaining a valuable point in the process, as the Irish defender, who has represented Republic of Ireland at under-19 level, latched onto Scott Bailey's knockdown inside the box but his resulting shot was blocked for a corner.
Newcastle United Under-21s: Aidan Harris, Leo Shahar (Harry Powell 68), Charlie McArthur, Cathal Heffernan (c), Alex Murphy, Isaac Hayden (Scott Bailey 61), Lewis Miley, Alfie Harrison (Mo Sedibeh 77), Darren Palmer (James Huntley 77), Johnny Emerson (Josh Donaldson 61), Ben Parkinson.
Subs not used: James Taylor, Ellis Stanton.