The 59-cap Weepu gets the No.9 jersey ahead of Alby Mathewson, who drops to the bench for a contest between two sides sitting near the foot of the table.
Weepu won a battle with his weight to be included in the All Blacks squad for the June series against Ireland, and went to play all three Tests as a substitute.
"Piri is back from an All Black campaign and his experience will certainly help us," coach Pat Lam said on Thursday.
In other changes to the line-up that began the Blues' last match almost five weeks ago, New Zealand Sevens star Charles Piutau will make his Super Rugby debut.
Piutau will play at fullback, where Lam's options have been reduced by injury.
Andrew Van der Heijden comes in at lock, a position where the Blues are also down in numbers.
Meanwhile, skipper Keven Mealamu makes his return, after the hooker ended a lengthy injury spell on the sidelines with his appearance off the bench in the final Test against Ireland.
Blues: Charles Piutau, Lachie Munro, Francis Saili, Ma'a Nonu, Rene Ranger, Michael Hobbs, Piri Weepu, Luke Braid, Daniel Braid, Steven Luatua, Andrew Van der Heijden, Liaki Moli, Tevita Mailau, Keven Mealamu (capt), Tony Woodcock. Res: Tom McCartney, Angus Ta'avao, Chris Lowrey, Peter Saili, Alby Mathewson, Orene Ai'i, Hadleigh Parkes.