Blair Kinghorn starts at fly-half and Ollie Smith is at full-back for Scotland's match with Australia.
With British and Irish Lion Finn Russell left out of Scotland's squad for the series, Edinburgh's Kinghorn is chosen at number 10.
Glasgow's Smith wins his second cap in the absence of Exeter's Stuart Hogg, while Jamie Ritchie captains the side.
Scotland's non-home based players are unavailable until after Saturday's four-game series opener at Murrayfield.
Backs Stafford McDowall and Kyle Steyn and forward Murphy Walker have been released to play in Glasgow Warriors' United Rugby Championship match against Benetton.
Jack Dempsey is a potential debutant off the bench while fellow replacement Damien Hoyland could make his first appearance in five years.
After the visit of former Glasgow Warriors head coach Dave Rennie's Wallabies, Gregor Townsend's Scots host Fiji (5 November), New Zealand (13 November) and Argentina (19 Argentina).
Scotland won two of their Six Nations matches in the spring before losing their summer tour series against Argentina with two defeats.
Ritchie has taken over as captain from Hogg and scrum-half Ali Price and lock Grant Gilchrist have been selected as vice-captains.
Scotland: Ollie Smith, Darcy Graham, Mark Bennett, Sione Tuipulotu, Duhan van der Merwe, Blair Kinghorn, Ali Price; Pierre Schoeman, Dave Cherry, Zander Fagerson, Sam Skinner, Grant Gilchrist, Jamie Ritchie (capt), Hamish Watson, Matt Fagerson.
Replacements: George Turner, Jamie Bhatti, WP Nel, Glen Young, Jack Dempsey, George Horne, Ross Thompson, Damien Hoyland.
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