Carlisle gained revenge for their earlier defeat against the U's by coming from behind themselves to win at Brunton Park.
The U's had taken on ten men for the whole of the second half, but were then a goal behind within seven minutes as the home side hit a quick fire double.
Despite late pressure, the U's were unable to rescue a point and whilst they stay five points inside the play-off zone, they will want - and need - to get back to winning ways soon.
U's boss Aidy Boothroyd rang the changes for the visit to Cumbria, with a host of pace and power in the team.
Ian Henderson made his first start for the club on the left, whilst Ashley Vincent made his first start since Swindon in September on the right hand side. David Fox came in after two months out of the starting eleven, whilst Kevin Lisbie made a rare start in 2010.
Anthony Wordsworth, Clive Platt and John-Joe O'Toole all started on the bench, whilst Kem Izzet was the fourth player to miss out as he began his two game suspension.
The U's started brightly and had an effort on goal within the first minute of the game. The ball dropped to Fox from Odejayi twenty-five yards from goal and his hooked effort went just over the roof of the net.
They followed that up by another chance on four minutes as the Carlisle defence failed to clear and Odejayi flicked it into the path of Lisbie. He set himself and hit a fierce volley, which Collin did really well to palm over the bar.
The U's had to defend firmly against some Carlisle pressure after those chances, but had the next chance on nine minutes as a corner from the right by Fox flashed across goal and Vincent only just missed making a connection in the middle.
The home side were dangerous when on the attack and should have been in front with eighteen minutes. Kavanagh put Price in and the striker went across goal with his shot and it slipped past the post when he probably should have scored.
Price went close again on 28 minutes with a cushioned volley from a ball on the right. He looked like he was set to lash the effort, but instead tried to help it on its way and it went wide of goal.
The U's were getting to the final third without really testing Collin, but Henderson could consider himself unlucky not to get closer to the cross that came to him from Odejayi on 33 minutes.
Price went into the book as he obstructed Williams taking a clearance from goal, whilst Henderson followed him in getting a yellow as he tugged back the marauding Keogh.
The home side were finishing the half strongly, but went down to ten men just before the break as Taiwo was dismissed for a second yellow card, as he tugged back Henderson.
The U's went close not long after the restart, Lisbie bursting down the left and cutting into the box, before curling an effort beyond the far post with two other players waiting in the area.
The dangerous Hurst was then substituted for the home team having taken a whack in the face from a Tierney clearance, with Marshall coming on.
Despite being down to ten men, the home side were not afraid to break down either flank with some attacking full back play, but the U's were holding firm.
The U's needed to start create things going the other way, though, and introduced two further changes with half an hour remaining.
He brought on Platt and Ifil for Odejayi and Vincent in an attempt to change things around, and Ifil's cross fell to Prutton, who, from a narrow angle, forced a good save out of Collin.
Platt did find a path to goal midway through the second half though. Lisbie burrowed his way past his man and, as the ball rebounded around the area, he slotted it home under the keeper.
But the lead lasted less than two minutes. This time it was Price who wriggled his way clear and cut it back to his man, who lifted the ball past Williams and into the net.
The home side had been lifted by their goal and went close again as they smacked a shot against the bar. But a minute later and they were in front, as a low cross at the near post found Price, he turned it past Williams.
Something occurred as the U's went in front and Abbott was sent from the touchline as his side reflected on taking the lead.
The right side was proving fruitful for the home side and Marshall again got in down that side with twelve minutes remaining, Marshall forcing a great save out of Williams.
Platt went close with a chance similar to his earlier goal. Ifil's bundling run into the box saw the ball roll out to the striker on the right hand side and his shot was smothered by the defender, before Collin jumped on it before it rolled in.
The U's pushed Heath up for the dying stages of the match, and had an extended spell of injury time to try and find a leveller.
But, despite late pressure, Collin was not seriously tested and the home side recorded a memorable win.