Crawley Town defender Mark Connolly scored a late consolation goal but this was not enough to prevent Reds suffering their second away defeat in a row.
They face a long journey home from Cumbria after three first half goals led to a 3-1 loss at Carlisle.
An early fifth-minute goal by Jabo Ibehre was added to before the break by Jason Kennedy and Luke Joyce.
Reds pushed forward in the closing staged in search of a goal and this came in the 90th minute through defender Mark Connolly.
Head coach Dermot Drummy made three changes to last weekend’s side which drew 0-0 with Accrington Stanley.
Aryan Tajbakhsh made his league debut and Adi Yussuf and Alex Davey started in place of Bobson Bawling, Billy Clifford and Joe McNerney.
Carlisle included two former Crawley players, Nicky Adams and Mike Jones.
Carlisle took the lead in the fifth minute when Tom Miller’s long throw from the right was headed in by Ibehre.
Crawley then created some good chances as they looked for an equaliser a James Collins had a cross cleared then saw a shot blocked before a follow-up up attempt by Kaby Djalo was scrambled away.
Skipper Jimmy Smith then kept the pressure on with a brilliant shot from long-range which keeper Mark Gillespie pushed around for a corner.
Reds keep attacking and a terrific run by Tajbakhsh led to a good through ball to Collins, who was desperately kept out by the home defence.
However Carlisle went 2-0 up in the 27th minute when Jones played a ball into the box for Michael Raynes, who headed down to Kennedy to score from two yards.
The home side increased their lead in fine style when Luke Joyce hit a stunning 25-yard shot in off the crossbar to send Reds into the half-time break with a mountain to overcome.
Carlisle were on the attack straight away in the second half as Charlie Wyke volleyed wide from a cross from Ibehre.
Moments later Yussuf went close after showing some deft footwork to keep clear of two defenders before putting his shot wide.
Crawley began to threaten as they looked to get on the scoresheet.
Boldewijn struck wide after being put in by Tajbakhsh, before Collins fired a free-kick over the bar from 25 yards.
From a counter-attack, Boldewijn crossed for Yussuf who headed over the bar.
Then Collins headed a cross from Lewis Young from the right over the bar.
Glenn Morris did well to save a shot by substitute Jamie Devitt as Carlisle looked for a fourth goal.
Collins twice have shots blocked and Bawling supplied Collins who headed wide as Crawley pushed for a late consolation goal.
This finally came in added-time when Boldewijn’s cross was tapped-in from short-range by Connolly.
REDS: Morris, Young, Davey, Connolly, Blackman, Boldewijn, Smith (capt), Djalo (Clifford 54), Tajbakhsh (Bawling 62), Collins, Yussuf (Banton 85)
Unused subs: Beeney, Arthur, Pappoe
CARLISLE: Gillespie, Joyce, Raynes (capt), Ellis, Kennedy, Jones, Wyke (S.Miller 74), Adams, Ibehre (Devitt 64), Brisley, T.Miller (Brough 56)
Unused subs: Asamoah, McKee, Lambe, Crocombe
REFEREE: Graham Salisbury
ATTENDANCE: 5,619 (66 away)
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