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David Tutonda scored the winning penalty as Gillingham reached the Carabao Cup third round.
After 10 perfect penalties, Gills keeper Jake Turner turned Exeter's sixth kick, taken by Josh Key, over the bar.
That gave Tutonda the chance to win it and he made no mistake with an ice-cool finish.
The tie went straight to penalties after a goalless 90 minutes, with League 2 Gills edging their League 1 opponents, both sides having made six changes for the match.
There was plenty of effort but not too much quality in a goalless first half that saw the sides cancel each other out.
For the Gills, Tutonda’s break down the left took him into the box, he drove the ball across the face of goal but there was nobody to tuck it away.
That summed it up for the Gills, a case of almost but not quite, with the hosts’ best chance of the half seeing Stuart O’Keefe head over from close range after Elkan Baggott nodded Alex MacDonald’s deep corner back across goal.
Olly Lee’s strike from distance, after Cheye Alexander played the ball infield, was well-held by Scott Brown, while Lewis Walker turned the ball from Will Wright’s cross after a nice spell of possession in the Grecians half.
Exeter had a couple of decent chances in the first half.
Early on, Tutonda made a key interception from Jake Caprice’s cross after a swift counter down the left, a break referee Carl Brook inadvertently had a hand in, when Matt Jay’s initial clearance hit his back and gave Exeter a second chance to get away.
Captain Jay later stabbed wide when the ball dropped kindly in the box, and Javani Brown dinked over the top after Turner came out of his goal to deny Caprice.
A fierce strike from Key was beaten away by Turner early in the second half, an awkward one to deal with for the Gills keeper with the speed it came at him.
Baggott had a strike blocked at the other end after another dangerous Tutonda cross, half-time substitute Ben Reeves forced wide after picking up the loose ball in the box as Gills.
Pressure continued, lifting the crowd in the process, and when Alexander worked the ball to MacDonald, a cracking cross was headed over by Lee.
Reeves fired over and MacDonald had a shot blocked, either side of Jay belting a strike over for the visitors from distance, midway through the half.
Baggott took a sore one in the face blocking Key’s effort with just over 10 minutes to play, while Wright put the ball wide for the Gills after Reeves swung over a free-kick to the back post.
There were chances at either end deep into six minutes of added time, Turner holding Caprice’s strike before substitute Jordan Green missed by inches after meeting a cross.
Lee, Mikael Mandron, Wright, Reeves and Hakeeb Adekulan all scored from the the spot for the Gills before Tutonda's clincher.
Gillingham: Turner, Alexander, Tutonda, Wright, Ehmer, MacDonald (Mandron 80mins), O’Keefe (Reeves 46mins), Lee, Walker (Green 81mins), Baggott, Kashket (Adelakun 89mins). Subs not used: Morris, Carter.
Exeter: S Brown, Caprice, Stubbs, Jay (Cox 73mins), Key, Dieng (Chauke 72mins), Kite (Collins 60mins), J Brown, Coley, Sweeney (Diabete 64mins), Grounds (Hartridge 72mins). Subs not used: Blackman, Spares, Nombe, Borges.
Referee: Carl Brook.
Attendance: 2,927 (257 away).