Jay Turner-Cooke netted twice within the opening half-hour at Whitley Park, with the 20-year-old attacking midfielder breaking the deadlock with a drilled close-range finish.
The attacking midfielder doubled his and United's goalscoring tally with a drilled effort from the edge of the box before Newcastle's youngsters, ultimately, recorded their first home win of the 2024/25 campaign.
O'Carroll made three changes from the side which suffered a narrow 1-0 defeat against West Ham United last week as Alfie Harrison, Dylan Charlton and Ciaran Thompson replaced Johnny Emerson, Alex Murphy and Cathal Heffernan respectively.
Targeting their first home win of the 2024/25 campaign, the young Magpies created the opening goalscoring opportunity as Parkinson, who made his Premier League debut for his boyhood club, latched onto Turner-Cooke's teasing cross but saw his stabbed effort towards goal held by Rovers goalkeeper Jack Barrett.
Parkinson was unfortunate not to fire Newcastle ahead minutes later as a neat move involving Leo Shahar and Alfie Harrison saw the latter thread a low cross into Parkinson's path, who steered a first-time volley over the crossbar.
In the 17th minute, Newcastle took the lead through Turner-Cooke. After Harrison's inviting cross to the byline was nodded into the six-yard area by Parkinson before the South Shields-born youngster drilled the ball into the roof of the net.
The 20-year-old, who spent the first-half of the 2023/24 campaign on loan at Scottish Premiership outfit St Johnstone, almost doubled his side's lead in quick succession after collecting Harrison's pass before his placed effort was held by Barrett.
Turner-Cooke, however, extended the hosts' advantage in the 30th minute, collecting Travis Hernes' quickly-taken free-kick before, with time and space, fired a fierce low attempt into the bottom right-hand corner.
Parkinson was unable to extend Newcastle's lead before the half-time whistle as the Durham-born teenager's stretching close-range header from Turner-Cooke's cross dropped over the woodwork.
In the second-half, Harrison went close to netting his first goal at under-21 level as the Keighley-born youngster, who joined the Magpies from Manchester City in Febraury 2024, latched onto a loose ball following Turner-Cooke's dangerous cross but lashed his effort over the crossbar.
Harris produced a key save to prevent Rovers from halving the deficit, scooping Aodhan Doherty's curling effort before Magpies defender Ciaran Thompson importantly cleared the ball to safety.
Newcastle were made to withstand attacking pressure from their Blackburn counterparts, with Dominik Biniek narrowly failing to connect with Lewis Bell's inviting low cross into the six-yard box.
United's youngsters were able to see out the contest, with Harris recording his second clean sheet of the 2024/25 season in the process, as O'Carroll's coaching reign got off to a positive start.
Newcastle United Under-21s: Aidan Harris, Leo Shahar (c), Ciaran Thompson, Charlie McArthur, Dylan Charlton, Anthony Munda (Ellis Stanton 59), Travis Hernes, Jay Turner-Cooke, Alfie Harrison (Josh Donaldson 69), Trevan Sanusi (Johnny Emerson 59), Ben Parkinson.
Subs not used: Cathal Heffernan, Tyler Jones.
