Campbell played the last of his four tests in Australia's first ever loss to Italy in Florence in 2022, but had an impressive season in Super Rugby.
James Slipper, Australia's most-capped test player, was named as replacement loosehead prop, confirming his return from retirement.
Centre Len Ikitau, flanker Tom Hooper as well as props Angus Bell and Taniela Tupou all return to Australian colours after playing club rugby in Europe.
Flyhalf Carter Gordon and scrumhalf Ryan Lonergan will start in the halves with Ben Donaldson and Tate McDermott backing up from the bench.
Lock Lachlan Shaw was named among the replacements and could make his test debut.
Loose forward Harry Wilson retains the captaincy for Saturday's match at Sydney Football Stadium.
Australia also host France and Italy in July's Southern Hemisphere section of the new competition.
"The group has reconnected quickly and we've worked hard over the past week to prepare as best we can for what is an exciting challenge against the number three team in world rugby," said coach Joe Schmidt.
Australia squad to face Ireland
Starters: 15–Jock Campbell, 14–Max Jorgensen, 13–Joseph-Aukuso Suaalii, 12–Len Ikitau, 11–Dylan Pietsch, 10–Carter Gordon, 9–Ryan Lonergan, 8–Harry Wilson, 7–Fraser McReight, 6–Rob Valetini, 5–Josh Canham, 4–Jeremy Williams, 3–Allan Alaalatoa, 2–Josh Nasser, 1–Angus Bell
Replacements: 16–Brandon Paenga-Amosa, 17–James Slipper, 18–Taniela Tupou, 19–Lachlan Shaw, 20–Tom Hooper, 21–Tate McDermott, 22–Ben Donaldson, 23–Tom Wright