From the 25th minute when man-of-the-match Steve Tosh headed the Borderers in front, there was little doubt about the outcome.
Thistle have come from behind to earn battling draws in both of the teams' previous meetings this season, but they didn't have the firepower to worry Gretna's solid defence.
David Graham scored Gretna's second, spinning round on a pass from Tosh to shoot into the bottom corner of the net after 37 minutes.
Inspirational Tosh added the third 10 minutes into the second half after good work by Gavin Skelton and John O'Neil.
Gretna keeper Alan Main was called on to make his only save of the game in the 63rd minute - diving one-handed to save a Ricky Gillies shot.
And Gretna went further in front with 15 minutes to go when Skelton lashed in number four, with Thistle's dejected fans heading for the exits in their hundreds.
A Scott McCulloch driven goal in the 80th minute was little consolation for Thistle, as Gretna went on to add two more in the final five minutes.
Substitute James Grady looped in a header from a Skelton cross, and Graham grabbed his second in the 90th minute.
Dejected Thistle manager Dick Campbell admitted afterwards:"From start to finish, Gretna were in total control of the game. Every time the ball came into the box, we looked liked losing a goal."