An own goal from John Egan led to Gillingham’s cup exit at Priesfield.
The Gills defender bundled the ball into his own net midway through the first half.
In the end, it was all that separated League 1 Gills and Premier League Newcastle.
Gills’ best chance of the game came with 20 minutes left as substitute Luke Norris forced keeper Tim Krull into a good save.
Last season’s top scorer Cody McDonald – back from injury - was one of four changes to the Gills XI as boss Peter Taylor looked to pull off a shock result against Alan Pardew’s Newcastle.
Josh Pritchard made his first start for the Gills, playing as a defensive midfielder alongside Jake Hessenthaler. Also added to the team was Callum Davies, who played in a back three.
The Gills were facing Newcastle for the first time since 1977 and early on they put the visitors under pressure.
But it was Newcastle who had the best of the first half chances, testing keeper Stephen Bywater with a couple of chances from Frenchman Emmanuel Riviere.
The opening goal came in the 23 minute when winger Gabriel Obertan guided a hopeful cross into the box and got lucky. John Egan got in the way but could only divert the ball past his own keeper.
It was the fourth own goal the Gills had scored already this season.
Gillingham’s best chance of the half fell to Matt Fish. He curled an effort with his left foot narrowly wide, with United keeper Tim Krul at full stretch.
The Gills made a swap at the break, with Aaron Morris replace Pritchard.
But with nine minutes gone of the second half Newcastle’s Massadio Haidara, with space, clipped the top of the bar from 30 yards.
Bradley Dack put a half chance over for the Gills while at the other end Gills keeper Stephen Bywater held onto Fabricio Coloccini’s powerful drive.
With 25 minutes left Taylor swapped his strikeforce, with Antonio German and Norris entering the action.
Norris came close to an equalising goal when he skipped past a Coloccini challenge before smashing a shot at goal. Krul tipped the effort over and watched as Egan headed the resulting corner wide.
German headed a late chance over but the Gills, who were never out of the tie, couldn’t find the net.
Gillingham: Bywater, Fish, Egan, Hause, Legge, Hessenthaler, Kedwell (Norris 65mins), McDonald (German 65mins), Pritchard (A Morris 46mins), Davies, Dack. Subs: G Morris, McGlashan, Dickenson, Hoyte.
Newcastle: Krul, Coloccini, Sissoka, De Jong (Perez 68mins), Aarons (Cabella 60mins), Haidara, Janmaat, Obertan, Taylor, Riviere (Gouffran 86mins), Abeid. Subs: Anita, Ferreyra, Elliot, Dummett.