The forward struck in the 19th minute at Ashton Gate, latching on to a brilliant through ball from fellow summer signing Mohamed Diame and firing home in front of around 2,500 travelling supporters.
And that proved to be enough to secure all three points for the Magpies - their second triumph in four days.
The win could have been more emphatic, with Isaac Hayden heading inches wide in the first period, substitute Ayoze Perez threatening in the second, and Gayle striking the foot of the post with another outstanding effort.
But it was a far from simple afternoon for Rafa Benitez's side, who put in an outstanding, resolute defensive performance - especially in the second half when their backs were against the wall for long spells - to record a first away win in more than eight months.
The game was less than three minutes old when fit-again Mohamed Diame had the first chance of the afternoon but dragged his ambitious 20-yarder well wide.
Bristol City responded and a spell of heavy pressure saw full-back Adam Matthews have a shot blocked before, seconds later, Lee Tomlin chipped over the bar from the edge of the area.
United looked comfortable and solid and should have broken the deadlock in the 16th minute when Hayden met Matt Ritchie's corner at the near-post, only to head down and inches the wrong side of the upright.
Gayle then struck a free-kick over the top but the front man made up for it almost immediately with the first goal of the game.
It started deep in Newcastle's half, with Chancel Mbemba winning a crucial interception and skipping past a couple of challenges before feeding Diame.
The Senegalese midfielder looked up before sending an inch-perfect ball over the top of the Robins' rearguard and into the path of Gayle. If his first touch was impressive, his second was even better, holding off a defender to rifle past Richard O'Donnell.
City almost equalised on 23 minutes when Luke Freeman's inswinging free-kick caused chaos in the Magpies' penalty area, but Hordur Magnusson's goalbound header struck his teammate Aden Flint, and Tammy Abraham was unable to bundle home the follow-up.
And that was it for meaningful first half action, with neither side able to carve out a chance of note before the break.
The hosts made a bright start to the second half and Jamaal Lascelles had to deflect Lee Tomlin's shot over the bar, before centre-back partner Mbemba also managed to get a crucial block on a Luke Freeman effort.
City were dominating possession and a series of corners were flung into the box, but the Newcastle back line - led superbly by captain Jamaal Lascelles - coped with every aerial ball that came their way.
At the other end, Perez was introduced from the substitutes' bench just past the hour mark and the Spanish forward almost made a rapid impact - sending a long-range effort not too far over after being picked out in space.
Gayle went even closer in the 71st minute, and within a lick of paint of doubling his - and the Magpies' - advantage.
Fed by Jack Colback's intelligent pass, the former Crystal Palace man turned his marker and sent a low, curling effort past the despairing dive of O'Donnell but against the outside of the upright.
With time ticking away, Bristol City threw everything at the visitors in search of an equaliser. Centre-back Aden Flint wasn't too far away with a header, while Tomlin sent a free-kick onto the roof of the net.
But Newcastle held firm to record their first away victory since December 2015, and a first clean sheet of the season.
