United travelled to South Yorkshire for a first league fixture with Barnsley since 1986.
And manager Paul Simpson made two changes from the side that lost against Oxford United, with Jack Armer and Paul Huntington both handed starts.
They replaced Jack Robinson and Corey Whelan whom dropped out the squad, while there was a return for Fin Back on the bench. He was joined among the substitutes by January signing Sean Grehan, who made the match day squad for the first time since joining on loan from Crystal Palace.
It was the Blues who began brightly and they had the first major chance of the game within the first minute. Dan Butterworth gambled on Jack Armer's clearance and found himself through one-on-one, only to see his powerful strike repelled by Barnsley stopper Liam Roberts.
And the forward had another sight of goal moments later - capitalising on a poor pass from Jack Shepherd and stealing possession on the edge of the box, but Butterworth swept his shot narrowly wide of the far post.
But the Blues wouldn't let Barnsley off the hook again and took the lead in the seventh minute. Luke Armstrong reacted quickly to intercept Roberts' attempted pass out and fired into the bottom corner from 25 yards to net his first goal for the club.
The hosts grew into the game and Jack Ellis had to slide in bravely to block Devante Cole's strike after he broke into the box after being fed through by John McAtee.
Carlisle, though, were in their groove and were creating the better of the chances. Patient build-up from Owen Moxon, Harrison Neal and Ellis allowed the latter to cross and his teasing delivery was met with a diving header from Butterworth which had Roberts beaten, but came crashing back off the post.
Moxon then made a crucial intervention at the other end, clearing over the bar as Cole looked set to convert following a corner.
United continue to push forward and apply pressure and they were forcing plenty of errors - McCalmont charging down a Roberts clearance before seeing his cross flash just in front of the on-rushing attackers.
Harry Lewis had to come out and block a Callum Styles shot but he was largely untested in the first half as the Cumbrians headed into the break ahead.
But as was perhaps to be expected, the Tykes came out the blocks quickly after the restart. Callum Styles had their first chance of note, curling a free-kick high of the woodwork from 22 yards.
Carlisle remained a threat though and Armstrong almost doubled his tally after Shepherd misjudged his header and allowed the strike to latch onto Lewis' kick. His strike looped over Roberts as he rushed off his line but dropped just the wrong side of the bar.
It was Barnsley who struck next though as they levelled the scores. Jordan Williams surged forward and picked out Cole who took a touch before firing into the far corner from the angle.
The Blues responded well and after McCalmont pinched possession, Neal sent an effort over from 25 yards in a signal of the visitors' continuted intent.
At the other end, Herbie Kane wasn't far away when he left fly from range while McAtee sent an acrobatic effort into the gloves of Lewis following a long throw.
And it was Kane who would hand his side the lead with just four minutes remaining. Adam Phillips went down under pressure in the box and referee Will Finnie pointed to the spot - with Kane then firing into the roof of the net from 12 yards.
From there on out, it was all Carlisle as they sought to restore parity. Substitute Jordan Gibson saw a shot blocked while Owen Moxon arrowed a strike from 30 yards only inches over.
Jon Mellish then couldn't send his header goalwards from a long throw in stoppage time and, despite the Blues' pressure, there was no late equaliser.
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Goals
Barnsley - Cole (58), Kane (86)
Carlisle United - Armstrong (7)
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Bookings
Carlisle United - Armstrong (81)
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Teams
Barnsley - Roberts, Williams, De Gevigney, Kane (Russell 90+1), Styles (Cosgrove 77), O'Keeffe (Cotter 46), Phillips, Shepherd, Cole, McAtee, Connell (Cadden 46). Subs: Killip, Lopata, Watters
Carlisle United - Lewis, Armer, Moxon, Lavelle, Huntington, McCalmont, Butterworth (Gibson 77), Ellis (Back 83), Mellish, Neal, Armstrong. Subs: Breeze, Garner, Charters, Maguire, Grehan
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Match officials
Referee – Will Finnie
Assistant Referee 1 – Matthew Sowerby
Assistant Referee 2 – Danny Guest
Fourth Official – Alan Clayton
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Attendance – 11,507 (883 away)
