Gillingham produced some spirited play at times, but lacked bite in front of goal as they fell to their tenth away defeat.
The Merseysiders had a bright opening and took the lead after just seven minutes. Paul McLaren netted with a fine shot from the corner of the box following a corner played short by Steve Jennings.
Tranmere doubled their advantage in the 14th minute. Calvin Zola shook off two tackles to beat Simon Royce with a well-struck shot from 20 yards.
Tranmere continued to make most of the running in the opening period. Jennison Myrie-Williams was just wide from 25 yards and then Zola missed the target before seeing a deflected shot well held by Royce.
The striker was also just wide from a Myrie-Williams cross approaching half-time.
Gillingham could not really get in a blow at the home goal. Gary Mulligan went closest with a header after 35 minutes, but home keeper Danny Coyne made a comfortable stop.
The Gills made a bright start to the second period with Adam Miller and Barry Cogan prominent in midfield. Miller saw a 30-yarder saved and then substitute Leroy Griffiths had an effort deflected for a corner.
Mulligan headed wide after an hour and Gillingham's chances of pulling back the deficit faded away.
Jennings brought a good near-post save from Royce, Gareth Taylor headed over from a Jennings corner and then Myrie-Williams just missed the target with a flighted effort.
Tranmere remained comfortable in defence with Ian Goodison in sound form.
Gillingham sent on Adam Bygrave and Stuart Lewis to try and liven things up in the 72nd minute, but the Merseysiders remained in control.