Argyle had gone into the match with a three point cushion over the other teams pushing to secure a play-off spot.
But although the Greens have stayed seventh – the final play-off position – eighth-placed Luton Town are now level on points with them after they beat Hartlepool 3-0.
John Sheridan’s side cannot afford another slip up now in their final two matches against Tranmere and Shrewbury.
Argyle went behind at Carlisle in the 29th minute when Gary Dicker scored with a long-range effort.
Despite being cheered on by 500 supporters who had made the longest trip of the season, the Pilgrims could not respond and five minutes into the second half Carlisle added a second courtesy of Billy Paynter.
Afterwards manager Sheridan pulled no punches about his team’s display.
“I’m not satisfied with the way we played, not one little bit,” he said.
“The game was there for the taking but there was no urgency. The way we played felt like a testimonial.”