This second successive defeat in the Hallmark Security League has seen Blackpool slip out of the first division play-off zone.
Blackpool welcomed back Callum Kirkland in goal after long-term injury, while Carlisle also had a change of keeper, with Lewis Casson making only his second appearance of the season.
Before kick-off there was a perfectly observed minute’s silence in honour of Jimmy Armfield.
The Cumbrians soon tested Kirkland, who made a low save to turn the ball around for a corner. City continued to dominate but didn’t really threaten until the half-hour, when Ryan Errington fired just over.
AFC were denied by the woodwork five minutes later, when Alex Taylor’s left-foot shot from Jack Williams’ pass rehit a post.
But City went straight up to the other end and split the home defence wide open, David Renyard pushing the ball past Kirkland before poking the ball into the empty net.
The visitors doubled their lead on the stroke of half-time, when another through-ball beat the defence and Rob McCartney scored.
Taylor fired over just after the restart but AFC did get back into the game on 65 minutes, when substitute Carnan Dawson scored from close range.
The hosts introduced top scorer Ben Duffield but could not force an equaliser and Carlisle wrapped up their fourth straight win over AFC 10 minutes from time, when Renyard netted his second.
This was Carlisle’s first win of 2018 and it sees AFC slip to eighth.
Blackpool: Kirkland, Caunce, Betteridge, Donaghy, Baird, Pickering, Bishop, Fishwick, Taylor, Williams, McKenna; subs; Speight, Nay, Dawson, Hargreaves, Duffield.