The French had more possession from the offset, but it took them until the 12th minute to put points on the board, when winger Benjamin Fall burst through a gap for a converted try.
Argentina didn't react, unlike last week, and didn't look likely to turn the score around. France omitted the basic errors that gifted Argentina tries last week and infuriated coach Phillipe Saint-Andre.
Three successful penalty kicks in the space of 11 minutes extended France's lead to 16-3 after 31 minutes, with Contepomi kicking a penalty in the 26th.
Two tries in the 10 minutes before halftime to Huget and Machenaud took the game beyond Argentina.
After the break, France didn't let up, with center Maxime Mermoz (56th), Huget (63rd) and flanker Alexandre Lapandry (68th) all touching down for their highest score and biggest margin against the Pumas in 63 years of contests.
Pumas flanker Tomas de la Vega scored a consolation try five minutes from the end.
Despite the defeat, Contepomi left the field to a rousing reception from the crowd.
He debuted for the Pumas in 1998 and has been the figurehead of the Argentine game since he took over the captaincy after the 2007 World Cup. He has said he will continue to play for Argentina, just not as captain.
Pumas coach Santiago Phelan made seven changes to the side which won last week to try and increase his options before making debuting in the Rugby Championship in August, when they will tangle with powerhouses New Zealand, South Africa and Australia.
Preparation had gone well before Saturday, with Argentina defeating Italy 37-22 two weeks ago and victory against France in the first test.
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France 49 (Yoann Huget 2, Benjamin Fall, Maxime Machenaud, Maxime Mermoz, Alexandre Lapandry tries; Frederic Michalak 5 conversions, 3 penalties), Argentina 10 (Tomas de la Vega try; Felipe Contepomi conversion, penalty). HT: 30-3
