Cambridge United 1 Carlisle United 0: Jack Armer and Alfie McCalmont were both sent off as Carlisle slumped at the Abbey Stadium.
Sub George Thomas headed the only goal for Cambridge in the 74th minute as the Blues paid the price for a dismal second half showing.
And their day went from bad to worse when, in the closing stages, Armer saw red for a second bookable offence, before a high challenge by McCalmont also saw him sent off by ref Sam Purkiss.
The bitter defeat saw the nine-man Cumbrians fall into the League One relegation zone after a promising start soon faded and Cambridge claimed a first league win in nine.
Carlisle had the better of the opening exchanges but couldn't make the most of some good openings, and Mark Bonner's side dominated the second half.
The decisive moment came when Thomas, nine minutes after coming off the bench, headed home Liam Bennett's cross amid a long spell of home dominance.
As well as the two red cards that followed, there was a further blow for Carlisle on the day as Fin Back was unable to start the game, pulling out of the warm-up injured, Ben Barclay taking his place in front of a 6,513 crowd which included 661 travelling fans.
Blues boss Paul Simpson initially named an unchanged side following Tuesday's win over Burton Albion - but was forced into a change 20 minutes before kick-off when Back withdrew.
Barclay was promoted to the side at right-back with Corey Whelan, not named in the initial 18, stepping up to the bench.
Fit-again McCalmont was back in United's squad among their subs.
Cambridge's XI was also unchanged but they were without a sub keeper thanks to Will Mannion suffering from illness. Ex-Blues striker John-Kymani Gordon began on the home bench.
Watched by prospective new owners Tom snr and Patty Piatak, Carlisle made a lively start and could have scored inside the first two minutes as a sweeping attack down the left saw Jordan Gibson and Armer combine before Dan Butterworth pulled his shot wide from useful space.
Moments later Joe Garner came close to setting up Sean Maguire, and Cambridge then survived a scramble as Butterworth and Maguire failed to latch onto Gibson's cut-back.
The home side found some good spaces on the attack at times, particularly Sullay Kaikai on the left, but their final ball was often lacking.
Paul Digby opened up on the break down the right but Carlisle cleared his cross, with Sam Lavelle often in the right place to deal with danger.
Barclay headed a Maguire cross wide and Gibson and Butterworth saw shots deflect behind as Carlisle continued to enjoy the better of the early exchanges.
Kaikai, at the other end, forced Tomas Holy into a save with his feet from a low cross while the keeper stood tall to hold a Gassan Ahadme volley.
Later, Gibson saw a free-kick deflect over the bar as things remained tight, Cambridge flashing a dangerous cross through the Blues' box with the final kick of a first half which had seen neither side show enough bite in the opposition box.
The home side came out sharper at the start of the second half and Carlisle saw Liam Bennett rifle a shot inches wide after Lavelle had blocked Ahadme's finish.
At the other end, Carlisle's travelling fans shouted for a penalty for handball as Danny Andrew blocked Maguire's cross, but only a corner was awarded.
Cambridge, though, were now making much more of the running and after Kaikai shot wide from outside the box, Simpson made a double change on the hour mark, McCalmont and Terry Ablade replacing Butterworth and Maguire.
The hosts, though, came close when Lankester fed Ahadme in the box but Jon Mellish came to United's rescue - then, after a triple Cambridge change, Holy got down well to deny Brophy.
Moments later, Liam Bennett curled a long-range attempt just over and Carlisle sorely needed an outlet in the home half by this stage.
It did not come - and then they were punished as United lost possession again, Cambridge swept onto it and Liam Bennett found Thomas in the middle to head clinically past Holy.
It was no more than the hosts had deserved and Carlisle had 15 minutes to lift their so-far turgid second-half display.
Simpson introduced Ryan Edmondson and Luke Plange, and the Blues could have levelled when Moxon found Ablade and the loanee cut the ball back for fellow sub McCalmont, but the midfielder missed his kick.
Cambridge then brought on Gordon to face his former club in the closing stages, the ex-Blues man applauded by many in the away end.
Things then took another bad turn for Carlisle as Armer, already cautioned for a first-half foul, pulled back home sub Kaikai and was shown a second yellow card on 83 minutes.
And in the second minute of added time they were reduced to nine when McCalmont's high challenge on Rigby brought a straight red from ref Sam Purkiss.
Carlisle entertained belated thoughts of a fightback amid 12 added minutes, United enraged as what appeared two clear fouls on Ablade went unpunished by Purkiss, who came in for strong stick from the away end.
But moments of very late pressure brought nothing, and Carlisle slid to 21st in the table, their opponents jumping to 14th.
Cambridge: Stevens, L Bennett, Andrew, Morrison, R Bennett, Digby, Brophy (Gordon 78), Lankester (Thomas 65), Cousins, Kaikai (Janneh 65), Ahadme (Okenabirhie 65). Not used: Rossi, May, Haunstrup.
Goal: Thomas 74
Booked: Lankester, R Bennett.
Carlisle: Holy, Barclay, Armer, Lavelle, Mellish, Guy, Moxon (Robinson 84), Butterworth (McCalmont 61), Gibson (Plange 75), Maguire (Ablade 61), Garner (Edmondson 75). Not used: Andresson, Whelan.
Booked: Armer. Sent off: Armer, McCalmont.
Ref: Sam Purkiss.
Crowd: 6,513 (661 Carlisle fans).
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