Nacewa has been named in a back-line that includes Brian O'Driscoll and Felipe Contepomi who will resume their centre partnership.
Ireland internationals Shane Horgan and Rob Kearney have been named on either wing. In the injury-enforced absence of Leo Cullen, former Wallaby scrum half Chris Whitaker will captain the side.
Looking forward to the league opener, Whitaker said: "There's no doubting that the Cardiff game will be a big test. They have a good strong forward pack who are very physical, but they also have a lot of very fast and mobile backs that like to take the ball on.
"We can't afford to ease into the game because there will be a massive increase in terms of intensity from our three warm-up games.
At this time of year, and with places up for grabs, there's naturally a bit of nervousness in the squad. But that's a good thing because it means that everyone is focused on getting one of the starting 15 shirts.
"There's more depth in all positions this year and I believe that we're going into this new season with the strongest panel we've had since I arrived.
In the pack for Saturday's game, Cameron Jowitt is named in a dynamic-looking back row alongside Ireland internationals Shane Jennings and Jamie Heaslip.
Meanwhile, Leinster Academy graduate Sean O'Brien could be one of two potential debutants should he be called upon in the Welsh capital alongside summer signing and former Ireland 'A' captain John Fogarty.
Prop Stephen Knoop has recovered from illness to take his place on a replacements bench which includes Ireland trio Trevor Hogan, Luke Fitzgerald and Girvan Dempsey.
LEINSTER (v Cardiff Blues): Isa Nacewa; Shane Horgan, Brian O'Driscoll, Felipe Contepomi, Rob Kearney; Jonathan Sexton, Chris Whitaker (capt); Cian Healy, Bernard Jackman, Ronan McCormack, Devin Toner, Malcolm O'Kelly, Cameron Jowitt, Shane Jennings, Jamie Heaslip.
Replacements: John Fogarty, Stephen Knoop, Trevor Hogan, Sean O'Brien, Chris Keane, Luke Fitzgerald, Girvan Dempsey.