Guylain Ndumbu-Nsungu and Andrew Crofts went close with early efforts before Gillingham's pressure was rewarded with a well-worked opener.
Gary Mulligan showed neat control before laying the ball off to Mark Bentley, who slotted home a low strike past Keiren Westwood's outstretched arm.
The home side continued to dominate but suffered a scare in the 23rd minute when Carlisle defender Peter Murphy found space in the area and turned before shooting narrowly wide.
Gillingham responded with Bentley dancing around Zigor Aranalde, before delivering a low cross that Ndumbu-Nsungu narrowly failed to convert.
The Gills continued to create chances after the break with both Mulligan and Crofts going close with headers. When United hit back, Kevin Gall latched onto Derek Holmes' neat flick only to see his header tipped onto the bar by the back-pedalling Kelvin Jack.
Moments later, full-back David Raven's dangerous cross eluded everyone as cracks began to appear in Gillingham's defence.
However, in the 89th minute, Mulligan tapped home a Matthew Jarvis cross to seal the win.
In the dying moments Gall blasted a decent chance against Jack's legs to complete a frustrating afternoon for Neil McDonald's men.