Latu is among four changes from the side that lost 37-20 against world champions New Zealand in their Bledisloe Cup encounter in Japan last month.
Lock Adam Coleman returns from a groin injury while flanker Jack Dempsey and centre Samu Kerevi join the starting lineup after being used from the bench against the All Blacks.
The 25-year-old Latu, whose only previous start was against France in November 2016, is rewarded by coach Michael Cheika for the impact he made in the past two tests against Argentina and the All Blacks despite being sin-binned in both matches.
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“I just think it’s an opportunity for Tolu, who’s had his ups and downs over the last few weeks but I’m a big believer in Tolu and giving him a chance at starting, which he hasn’t had this year I don’t think,” Cheika told a news conference on Thursday.
Dempsey and Kerevi also showed enough against New Zealand to start at the Principality Stadium on Saturday.
"Dempsey was quite abrasive when he came on in the last game," the coach said.
"He didn’t play a lot of time but it’s a good opportunity for him now, with three big games left in the year to have a starting role and re-acquaint himself with test footy.
"He was showing good form at training which is all I’ve really seen him in, those couple of weeks, and I thought it was worthwhile giving him an opportunity last week and I think he showed that he’s ready to take another step forward."
Kerevi’s inclusion means that Israel Folau is shifted back to the wing.
Coleman missed the last game, but Cheika said he had no hesitation in slotting him back in.
“He’s become a mainstay inside of the team and now I think that’s ... for other players in that position to lift their game to try to challenge those two players who have a locking position."
Team: 15-Dane Haylett-Petty, 14-Israel Folau, 13-Samu Kerevi, 12-Kurtley Beale, 11-Sefa Naivalu, 10-Bernard Foley, 9-Will Genia, 8-David Pocock, 7-Michael Hooper (captain), 6-Jack Dempsey, 5-Adam Coleman, 4-Izack Rodda, 3-Allan Alaalatoa, 2-Tolu Latu, 1-Scott Sio
Replacements: 16-Tatafu Polota-Nau, 17-Sekope Kepu, 18-Taniela Tupou, 19-Rob Simmons, 20-Ned Hanigan, 21-Nick Phipps, 22-Matt To'omua, 23-Jack Maddocks
(Reporting by Mark Gleeson; Editing by David Goodman and Toby Davis)
