United travelled to Northampton Town in their latest League One fixture.
And manager Paul Simpson made one change from the side that faced Lincoln City on Easter Monday as January signing Georgie Kelly was handed a first start.
And it was the striker who threatened first for the Blues, taking down the ball on the edge of the area and drilling wide after a positive opening from the visitors.
He would come closer still midway through the half, connecting with Harrison Neal's cross and forcing home stopper Lee Burge into a fine fingertip stop as his glancing header looked set to find the net.
Dan Butterworth then fired wide from range before Will Hoskins threatened first for the Cobblers as he blazed over after finding space 20 yards out.
But having weathered much of United's pressure, Northampton took the lead against the run of play - Kieron Bowie reacting quickly to turn home from close range after a dangerous corner.
Luke Armstrong came close to a leveller before the interval but Burge was equal to his header as Northampton went in ahead at the break.
And the hosts started the second half brightly as they sought a second, with Jon Guthrie sending an early header over the bar from another set piece delivery.
Sam Sherring turned a deep free-kick behind at the back post as the Cobblers kept asking questions of the Blues, with Harry Lewis getting down well to hold substitute Tony Springett's driven strike as the half drew on.
United showed plenty of willingness to get forward in search of an equaliser but were met with a stubborn Northampton rearguard who gave little away.
Guthrie had to make a crucial late intervention to stop Jack Diamond turning home and from the resultant corner, the hosts broke through Ali Koiki who rounded Lewis and slotted home to wrap-up the victory.
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Goals
Northampton Town - Bowie (33), Koiki (90+4)
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Teams
Northampton Town - Burge, Odimayo (Koiki 46), Guthrie, Sherring, McGowan (Willis 79), Fox (McWilliams 72), Leonard, Pinnock, Bowie, Appere (Springett 79), Hoskins (Sowerby 72). Subs: Simpson, Moulden
Carlisle United - Lewis, Armer, Lavelle, Kelly (Diamond 57), Butterworth (Maguire 32), Ellis (Emmanuel 83), Robinson (Harris 83), Mellish, Barclay, Neal, Armstrong. Subs: Breeze, Back, Huntington
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Match officials
Referee - Ross Joyce
Assistant Referee 1 - Marc Wilson
Assistant Referee 2 - Steve Durnall
Fourth Official - Kenwyn Hughes
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Attendance – 6,328 (335 away)