Scarlets wing Steff Evans, Gloucester back Owen Williams and Cardiff Blues flanker Josh Navidi, who have just six caps between them, are all probable starters at the Principality Stadium.
Scarlets flanker Aaron Shingler is also thought to be in contention for the autumn series opener as Wales target a first victory over the Wallabies since 2008.
Evans is expected to take over from an injured George North, with Williams filling the inside centre role alongside fly-half Dan Biggar as Gatland opts for two midfield playmakers in a change of tactical emphasis.
Navidi, meanwhile, seems poised to fill the openside berth with Sam Warburton and Justin Tipuric both injured, and there could be roles among the replacements for uncapped Ospreys pair Owen Watkin and Sam Cross.
Wales have suffered 12 successive defeats against Australia — seven of those in Cardiff — which is the record facing them as they embark on an autumn schedule that also features Georgia, New Zealand and South Africa.
Speaking when he announced his 36-man autumn Test squad, Gatland said: “We changed the way we played in New Zealand in 2016, and it’s always hard.
“When you are a club side, you have a pre-season and more time together, and we have always felt we’ve done well in World Cup campaigns because we’ve had more time together.
“It might take a little bit of time as we try to change our approach with the midfield. It might not happen from day one, but we’ve just got to be a little bit patient. We need to be bold, go down that path and commit to it.
“Our mindset has to be that we are comfortable with going three-four minutes’ ball in play time where if we are defending and there is a turnover, the first reaction is not to kick the ball but be attack-focused.
“Despite what people may report sometimes, the message to our players constantly is that we want them to play what is in front of you, we want you to be attack-focused, we want you to take risks because that is what you have to do.
“If it means shifting the ball on your own goal-line, you are encouraged to do that. If you ask the players if they have ever been strait-jacketed or put in a stranglehold, they will say no. They are told to play what is in front of them and express themselves.”
Considerable excitement surrounds Evans’ potential call-up, having scored 26 tries in 67 appearances for the Scarlets and underlined his ability to consistently test defences.
“Steff has got great feet and he scores tries,” Gatland added. “He pops up off nine and 10, and at the back of rucks.
“His ability to off-load makes him the sort of player you are looking for. We have always encouraged our wingers to increase their number of touches, so we are pretty excited by him.”