Carlisle boss Greg Abbott was left dejected as Tom Pope's injury-time strike gave Port Vale a 1-0 win.
The striker, who scored 33 times last year, snatched the winner two minutes into stoppage time to seal the three points for the visitors.
Abbott said: "I'm pretty despondent with the end result. We should have scored in the last 30 seconds. We didn't and they did. The game is cruel and we wanted to win for the fans who stuck by us.
"They got a break right at the end. We will play worse and win games. If our chance had gone in it would have been a different result.
"With the game petering out I would have taken a point. We need a result to give us belief."
Lee Miller came within inches of giving Carlisle an early lead when his header from James Berrett's cross came back off the bar with Vale goalkeeper Chris Neal beaten.
One of Carlisle's new boys, on-loan Swindon defender Troy Archibald-Henville, missed a great chance three minutes before half-time, heading Berrett's corner over the top from inside the six-yard box.
Danger signals flashed for Carlisle straight after the break when Louis Dodds' shot on the turn looked to be going in until Danny Livesey cleared off the line.
But just when it seemed the game was heading for stalemate, with Carlisle still seeking their first win of the season and Valiants looking for a first away win, up popped Pope to settle it in added time.