A number of youngsters were included in the Seasiders matchday squad, but it was a brace from the experienced Jake Beesley that proved to be the difference at Bloomfield Road.
The Seasiders will be back in action in the competition at the beginning of December, while the Shrimps finish the group in third behind Liverpool U21s, despite getting a late goal through Farrend Rawson.
Following a quiet opening period, Blackpool took the lead in the 22nd minute.
With his back turned away from goal, Beesley got on the end of a Jensen Weir cross to guide a volley past Adam Smith in the Shrimps net.
Chances continued to be limited throughout the first half, with an easy save from an Andy Lyons shot from distance being the closest either team came to getting the second goal of the game before the break.
Following the restart, the Seasiders quickly doubled their lead.
Beesley met another cross from the left side, with the striker using his head this time to beat the Morecambe keeper.
The visitors’ best effort came on the hour mark, as JJ McKiernan struck the top of the crossbar with a close-ranged attempt.
Down the other end, substitute Tayt Trusty came close to extending Blackpool’s lead, with his effort being cleared off the line.
Shortly after, the youngster was forced off on a stretcher after suffering what appeared to be an ankle injury.
Morecambe pulled a goal back in stoppage time, with Rawson heading past Richard O’Donnell to make it 2-1- which is how things finished.