Second-half goals from Preston's Keith Keane and Josh Brownhill consigned Gillingham to defeat in
Peter Taylor's first match as interim manager.
Keane broke the deadlock when he latched onto a quick throw-in and his low shot crept inside the far post.
After Chris Whelpdale squandered two chances to equalise, a superb run and lay-off from Stuart Beavon set up Brownhill to sidefoot home.
Danny Kedwell pulled one back when he headed in from a Whelpdale free-kick.
The Gills almost grabbed a point late on, but Kedwell headed into Declan Rudd's hands and Joe Martin had a shot blocked in injury time.
Taylor, who led Gillingham to promotion to the second tier in 1999-2000, returned to Priestfield this week following
the sacking of Martin Allen last Sunday.
VIEW FROM THE DRESSING ROOM
Gillingham interim boss Peter Taylor told BBC Radio Kent:
"I think there were some good bits and some disappointing bits.
"Overall I was very pleased, we passed the ball well, created some decent chances which on another day would have gone in.
"I said to the players, no dropping of the heads because the way we finished we could have got some goals. It could have been a point which would have been a much happier evening."
Preston manager Simon Grayson told BBC Radio Lancashire:
"It was a game that, for 60 minutes, we were cruising. We controlled the first half and just needed to up the tempo in the final third.
"We got the two goals, but their goal changed it and they went for it.
"For the last five minutes, we were hanging on a bit. We hung in and got three points."
Gillingham 01 Nelson 23 Harriman 03 Martin 07 Whelpdale 06 Legge 26 Barrett 12 Gregory 19 Hollands (Akinfenwa - 88' ) 10 McDonald (Weston - 57' ) 09 Kedwell 18 Lee Booked (German - 66' ) Substitutes 04 Linganzi 05 Davies 08 Akinfenwa 11 Weston 15 Dack 16 German 21 Howard Preston North End 23 Rudd 07 Humphrey (Holmes - 92' ) 03 Laird 06 Wright 04 Huntington 05 Clarke Booked 02 Keane Booked 19 Welsh 30 Brownhill (Byrom - 70' ) 10 Beavon (Buchanan - 85' ) 09 Davies Substitutes 01 Stuckmann 11 Holmes 13 Byrom 14 Garner 16 Buchanan 21 Mousinho 27 Hume