A second half fight back proved to be too little too late as confident Northampton made the best of their chances to extend their run to 13 games unbeaten at the expense of a home side who wasted some good openings along the way.
The nippy Derek Asamoah had Smith worried as United got the ball forward early but the keeper was out of his box quickly to hook the through ball away.
Determination from Grainger twice put him in possession inside the visiting half and another neat through ball left Asamoah with just one to beat. He dropped a shoulder and ignored the calls from Ibehre as he dragged a poor effort wide.
Northampton sent a warning message of their own when a huge ball forward bounced inside the box. Collins threw a leg at it and Gillespie had to go full length to fingertip it past the upright.
The Cobblers went close again when a Byrom free kick dropped nicely at the back stick. Buchanan showed first and his glanced header had to be plucked out of the air by the alert United stopper.
Carlisle showed they could be just as effective with their set pieces when Grainger bent a lovely ball into the six-yard box. Raynes stretched but it stuck under his feet and Smith was able to scoop it up before it could cross his line.
Ibehre had a finish from a lovely move chalked off for offside on the quarter hour, and Northampton pounced to make it count with a quick ball to Martin. He stepped inside and sent a cross into the box which Collins nodded into the net from close range.
United should have been back on level terms almost immediately when Ibehre pulled wide to deliver the cross. It looked to be perfect for Kennedy but he somehow touched his volley wide as he rose to meet it.
Long range efforts from Holmes and Buchanan followed as Northampton settled into a stride, but Carlisle went close when Grainger combined with Joyce and Hery to get to the edge of the area. He spotted Ibehre on the move but the big striker couldn't quite get enough on it as he sent a volley on the move into the side netting.
Carlisle were guilty of switching off for the second phase of another free kick when a half clearance was whisked back into the box. O'Toole helped it on and two deflections left Gillespie with no chance as it spun agonisingly past his outstretched leg.
Lady luck completely deserted the home side again at the other end as they tried to respond in kind when a Grainger cross came to Hery. He set it for Joyce to strike and a powerful shot struck Diamond and screwed past the target.
A raking 40-yard pass from Ellis brought yet another good chance as Prosser lost the flight of the ball, but Asamoah hesitated and it skipped off the surface before he could react. Ellis then had to do his defensive duties as Marquis pulled across the 18-yard box to take a pot-shot. It was heading in until the defender got his thigh in the way.
Asamoah bulged the side netting with a near post header from a Grainger corner as United kept trying to up the pace, but the half ended with more frustration as Hery and Buchanan went into the book for a tussle on the touchline.
A double substitution after the break had an immediate impact as Jabo Ibehre found himself with time on his hands on the right hand side of the 18-yard box. He took two touches and fizzed a fantastic cross into the area and the first touch of the day for Hallam Hope was a lovely strike which angled into the roof of the net.
Tails were up and Asamoah twisted and turned following more good work from Hope as he tried to find a way through. He had support but he lost his balance and popped his shot past the post.
Carlisle had only themselves to blame when their resurgence was derailed when a weak Holmes pass was allowed to skip unchallenged into the box. O'Toole slid in to apply the slightest of touches to help it on its way into the back of the net.
A thunderbolt from Martin wasn't too far away to adding to the lead, but Gilliead went close at the other end with a 35-yarder which dipped into the stands.
Gillespie had to be at his best when Marquis burst through one-on-one, but he needed help from Grainger when the same player pounced on the loose ball from the rebound to try to sweep it into the waiting net.
It was end-to-end and Raynes wasn't too far away when he jumped to meet a set piece from Grainger. The clearance from that was picked up by Atkinson and Raynes was even closer as he guided a header on the leap over the angle of post and bar.
A bad day became an afternoon to forget for the hosts when they were carved open with some fast play. Collins crept into the box and smashed a screamer into the far corner as Gillespie tried in vain to get a touch.
Smith saved from Raynes when his header threatened to go in from a Grainger free kick, and Kennedy claimed a goal, ignored by the officials, as he hooked it back at the keeper from a very tight angle. It hit a shoulder and the underside of the bar before the stopper was able to recover and pull it into his chest.
Hope had a shot from the left flank late in the day which went straight at Smith, but the leaders saw the job out as they protected their points gap at the top of the table.
United - Hope (46)
Northampton - Marquis (16), O'Toole (33, 59), Collins (74)
United - Hery (45), Atkinson (65)
Northampton - Buchanan (45), Marquis (82)
Carlisle United - Gillespie, Atkinson, Raynes, Ellis, Grainger, Gilliead, Joyce (McQueen 44), Kennedy, Hery (Hope 44), Asamoah, Ibehre. Subs - Bacon, Archibald-Henville, Rigg, Thompson, Gillesphey.
Northampton Town - Smith, Moloney, Diamond, Byrom, Holmes (Taylor 90), Buchanan, Collins, Martin (D'Ath 72), O'Toole, Prosser, Marquis (Hoskins 85). Subs - Clarke, Cresswell, Adams, Rose.
Referee - Mr David Coote
Attendance - 4,892 (457 away fans)