United were made to pay for a string of missed chances as Plymouth grabbed a late first half stunner and then went on to rub salt into the wounds with some clinical finishing after the break.
The game started well for Carlisle but an early attack broke down when a Joyce cross was cleared. That invited Wylde to go on a run and he carried it to the edge of the box from his own half. He went for goal but his shot was way too high.
United looked good going forward and a raking 40-yard pass from Grainger found Wyke breaking through. His touch was heavy and McCormick rushed off his line to gather.
The blue shirts stayed forward and good work from Ibehre earned a corner as Hartley struggled to deal with a loose ball. Grainger sent it deep and Kennedy was a whisker away as his downward header skimmed the outside of the post.
The visitors looked by far the more composed outfit and a slick build up involving Joyce and Kennedy left Ibehre with time to cross. A half clearance kept the pressure on and the big striker eventually scuffed a shot at the closing defender as Wyke slid him through.
A neat pass from Grainger kept things moving and it invited Osei to take his man on. Ibehre almost capitalised as the through ball ran loose. Nelson had to cover to stop the big man from tucking it in.
Former-United man Jake Jervis had two stabs at a high ball, as Plymouth tried to counter, but his first effort was blocked and he sent his poor follow up into the side netting.
A wild shot from Graham Carey followed before Carlisle started to reassert themselves with some incisive forward play. A floated ball from Joyce almost unlocked the door when Ibehre found himself in acres of space. McCormick was beaten and much-relieved to see the ball smash back to safety off the upright.
The Pilgrims couldn't get out of their own half and an exchange of passes between Kennedy and Ibehre allowed Joyce to edge forward. His rushed shot lacked direction and the home side gratefully hooked it clear.
Plymouth had to defend in numbers and rifled efforts from Balanta and Ibehre were smothered before Grainger stepped in to let fly. McCormick readjusted and showed comfortable hands.
The hosts enjoyed a better spell ahead of the break and Carey opened things up when he fed off Jervis. His shot had power but Gillespie readjusted to pull it into his chest.
Carlisle picked up the pace and Osei kept his cool to beat a man and sweep a low ball in. Kennedy side footed it and Hartley had to slide on the stretch to deflect it away.
The visitors looked the more likely and they thought they'd done the deed when Balanta challenged on the edge of the area. It squirmed free and Joyce was a millimetre wide with a rasping volley that had McCormick beaten.
But United were made to pay for their misses when former-Blues forward Jervis spun his man and bore down on goal. He put his boot through an unstoppable shot which angled into the top corner.
Long throws from Miller caused problems in time added on for the half and his first delivery, which bounced on the six yard line, was just too high for Ibehre to finish off. His second lob eventually fell in front of Balanta but he couldn't keep his swiped effort down.
The Pilgrims upped the tempo after the break and they doubled their lead following heroics from Grainger which stopped Reid from slotting the ball in as the pacey forward broke through. The Blues fell asleep for the corner delivery and the predatory Reuben Reid said thank you very much as he nodded a flick on into an empty net.
The night got worse as Graham Carey sprinted clear to clip the ball past the advancing Mark Gillespie, and Jake Jervis doubled his tally when he was given the same kind of clear run. The keeper got a boot to it but he couldn't stop it from bulging the onion bag.
Raynes went close with a near post glancing header late in the day, and Kennedy poked an Asamoah cut back over the bar from just 8 yards out as United seemed to accept their fate.
But Joe Thompson grabbed a late consolation with the last kick of the game when he finished an Hery cross on the volley from close range.
Plymouth - Jervis (44, 65), Reid (53), Carey (56)
United - Thompson (90)
Plymouth - McCormick (90)
Plymouth - McCormick, Mellor, Sawyer, McHugh, Nelson, Hartley, Reid, Carey, Wylde (Simpson 46), Jervis (Tanner 77), Boateng (Brunt 72). Subs - Bittner, Cox, Harvey, Purrington.
United - Gillespie, Miller, Raynes, Grainger, Balanta (Hery 76), Kennedy, Joyce, Dicker, Osei (Thompson 60), Ibehre, Wyke (Asamoah 76). Subs - Hanford, Archibald-Henville, Rigg, McQueen.
Referee - Mr Oliver Langford
Attendance - 6,071 (169 away fans)