The Brisbane-born Kris Burton, who has produced some impressive displays for Benetton Treviso this season, has been rewarded with the number 10 jersey.
The game will mark Burton's Six Nations debut and first appearance for Italy since he won his fourth cap against New Zealand in June 2009.
He comes in for the benched Luciano Orquera, in the only change to the back-line from the Fiji fixture. Treviso's Edoardo Gori will win his third successive cap at scrum half.
Italy's number 10 from last year's Six Nations, Craig Gower, has been ruled out with knee ligament damage, while a shoulder injury has sidelined influential flanker Mauro Bergamasco.
Leonardo Ghiraldini, Santiago Dellape and Josh Sole return in the forwards, with Fabio Ongaro, Carlo Del Fava and Robert Barbieri making way.
Parisse's availability at number 8 is a real boost to the Italians after he missed the 2010 Championship with a serious knee injury. He dislocated his finger in action for Stade Francais last week, but has been passed fit to face Ireland.
Parisse will captain the Azzurri from the back row, with Sole slotting in at blindside flanker and Alessandro Zanni moving to the openside berth.
Head coach Nick Mallett said: "Each year for us it's difficult. The Six Nations is a complicated tournament and it is not an issue to do with the calendar.
"We simply have to continue to improve. We will of course go out on the pitch trying to win all of our games.
"Our front row is among the strongest in the world with props like (Martin) Castrogiovanni, (Salvatore) Perugini and (Andrea) Lo Cicero. Also we have a very strong back row, and it will be interesting to see how (Edoardo) Gori will do in the tournament."
He added: "Gower and Mauro are two players that have great experience, but their absences open up a possibility to see new players at a high level.
"In the back row, Barbieri did very well in November, just as (Paul) Derbyshire did, while Orquera put in two good performances against Australia and Fiji and I believe it's time to see Burton, who right now is the Italian out-half that is playing best in the Magners League."
ITALY Team & Replacements (v Ireland, 2011 RBS 6 Nations Championship, Stadio Flaminio, Saturday, February 5, kick-off 3.30pm local time/2.30pm Irish time):
15. Luke McLean (Benetton Treviso)
14. Andrea Masi (Racing Metro 92)
13. Gonzalo Canale (Clermont Auvergne)
12. Alberto Sgarbi (Benetton Treviso)
11. Mirco Bergamasco (Racing Metro 92)
10. Kris Burton (Benetton Treviso)
9. Edoardo Gori (Benetton Treviso)
1. Salvatore Perugini (Aironi Rugby)
2. Leonardo Ghiraldini (Benetton Treviso)
3. Martin Castrogiovanni (Leicester Tigers)
4. Santiago Dellape (Racing Metro 92)
5. Quintin Geldenhuys (Aironi Rugby)
6. Josh Sole (Aironi Rugby)
7. Alessandro Zanni (Benetton Treviso)
8. Sergio Parisse (Stade Francais) (capt)
16. Fabio Ongaro (Aironi Rugby)
17. Andrea Lo Cicero (Racing Metro 92)
18. Carlo Del Fava (Aironi Rugby)
19. Valerio Bernabo (Benetton Treviso)
20. Pablo Canavosio (Aironi Rugby)
21. Luciano Orquera (Brive)
22. Gonzalo Garcia (Benetton Treviso)