The 35-year-old former Leinster back, currently at Stade Francais, sat out the Rugby Championship due to an agreement between the Argentinian Rugby Union (UAR) and the French clubs and was not named in coach Santiago Phelan's initial squad for this tour.
But with Biarritz centre Marcelo Bosch unavailable due to his own club commitments this weekend, Contepomi comes back into Phelan's starting XV to win his 79th cap as part of a side showing six changes and two positional switches from the defeat to Australia.
Alongside Contepomi in midfield will be former Harlequins and Stade Francais three-quarter Gonzalo Tiesi, who will make his first appearance since the 2011 World Cup.
Star fly-half Juan Martin Hernandez has been shifted to full-back, the position where he made his name, with Bordeaux-Begles' Nicolas Sanchez preferred in the number 10 role.
Lock Patricio Albacete is an injury absentee after suffering a fracture near his eye, with flanker Julio Farias Cabello moving into the second row to partner Manuel Carizza and Leonardo Senatore coming into the back row.
In the front row Leicester's Marcos Ayerza benefits from the retirement of Rodrigo Roncero and the absence of Gomez Kodela to start on the loosehead side of the scrum alongside Eusebio Guinazu and Juan Figallo.
Juan Imhoff is rewarded for his impressive form during the Rugby Championship and for Racing Metro as he takes the left wing slot from Bath's Horacio Agulla, with Exeter's Gonzalo Camacho on the other flank.
Juan Martin Fernandez Lobbe captains the side from number eight and is set to win his 50th cap.
Argentina team to play Wales at the Millennium Stadium on Saturday, November 10 (kick-off 1430):
JM Hernandez (Racing Metro), G Camacho (Exeter), G Tiesi (San Isidro), F Contepomi (Stade Francais), J Imhoff (Racing Metro), N Sanchez (Bordeaux-Begles), M Landajo (San Isidro), M Ayerza (Leicester), E Guinazu (Southern Kings), J Figallo (Montpellier); M Carizza (Racing Metro), JF Cabello (Tucuman); L Senatore (Gimnasia Rosario), JM Leguizamon (Lyon), JM Fernandez Lobbe (Toulon, captain).
Replacements: A Creevy (Montpellier), B Posiglioni (La Plata), J Gomez (Los Matreros), T Vallejos (Scarlets), T Leonardi (San Isidro), N Vergallo (Southern Kings), H Agulla (Bath), J Tuculet (Grenoble).
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