Full-back Horacio Agulla, winger Francisco Leonelli, centre Miguel Avramovic and number 8 Juan Manuel Leguizamon all come into the side, with Bernardo Stortoni, Gonzalo Tiesi, the injured Felipe Contepomi and Esteban Lozada making way.
There are a number of positional switches also. Federico Martin Aramburu moves from the right wing to partner Avramovic at centre, Rimas Alvarez Kairelis reverts from the back row to the second row and team captain Juan Martin Fernandez Lobbe shifts from number 8 to openside flanker.
The Pumas team includes 14 European-based players, eleven of whom play their club rugby in France.
Blindside flanker Martin Durand is the only home-based player to get a start. He is affiliated to the Champagnat club in Buenos Aires.
Looking forward to the final game of the tour, Fernandez Lobbe said: "Ireland are very tough opponents. They have very good side and combinations throughout the side.
"We must be very focused on our job if we want to secure a good result. We want to win, that's our main goal. I hope we can achieve it."
Despite losing both Rafael Carballo and Rodrigo Roncero to yellow cards in Turin last Saturday, Argentina still pulled through to beat the Italians and record their first win of a three-match European tour.
Phelan's men lost 12-6 to France in Marseille the previous Saturday.
ARGENTINA TEAM & REPLACEMENTS (v Ireland, GUINNESS Series 2008, Croke Park, Saturday, November 22, kick-off 2.45pm):
15 - Horacio Agulla (Brive)
14 - Francisco Leonelli (Saracens)
13 - Federico Martin Aramburu (Dax)
12 - Miguel Avramovic (Montauban)
11 - Rafael Carballo (Castres Olympique)
10 - Juan Martin Hernandez (Stade Francais)
9 - Nicolas Vergallo (Dax)
1 - Rodrigo Roncero (Stade Francais)
2 - Mario Ledesma (Clermont Auvergne)
3 - Juan Pablo Orlandi (Rovigo)
5 - Patricio Albacete (Toulouse)
6 - Martin Durand (Champagnat)
7 - Juan Martin Fernandez Lobbe (Sale Sharks) (capt)
8 - Juan Manuel Leguizamon (Stade Francais)
16 - Alberto Vernet Basualdo (Toulouse)
17 - Marcos Ayerza (Leicester Tigers)
18 - Esteban Lozada (Toulon)
19 - Alvaro Galindo (Racing Metro)
20 - Agustin Figuerola (CASI)
21 - Santiago Fernandez (Hindu)
22 - Bernardo Stortoni (Glasgow Warriors)