Second-half tries by Juan Imhoff and Gonzalo Camacho proved the difference as the Pumas recorded only their second win in Wales – their previous being 11 years to the day of their latest exploit.
Following their involvement in the Rugby Championship there were fears in Wales that the South Americans could catch the Grand Slam champions cold.
And they took full advantage with a pair of scintillating tries from their wings to bring Wales crashing down to earth and end any hopes of them climbing to fourth in the world rankings which would have seen them be seeded top of a 2015 World Cup pool.
"This is a great win for us and coming as it does 11 years to the day since we last beat them in Wales," said Argentinian captain Juan-Martin Fernandez Lobbe.
"We have been searching for this win for what is a new and younger squad to the one that played in last year's World Cup.
"It is a hugely significant win and against the Six Nations Grand Slam winners an extra special one."
Wales were without several of their Grand Slam stars with Adam Jones, Dan Lydiate, Ryan Jones and Jonathan Davies all ruled out through injury.
Aaron Jarvis slotted into the front row to make his debut while Tavis Knoyle was preferred to Mike Phillips at scrum-half.
Jamie Roberts, who will leave Cardiff Blues at the end of the season, lined up at inside centre opposite Felipe Contepomi, who inspired the Pumas to victory in 2001.
The veteran play-maker sat out the recent Rugby Championship but was recalled for the autumn series and opened the scoring on three minutes after Ian Evans was penalised for a high tackle.
Wales quickly hit back through Halfpenny, after Jarvis settled any early nerves with a penalty earned at the scrum, but Argentina regained their lead thanks to a Nicolas Sanchez drop-goal.
Sparking the game
But Argentina were dealt a major blow on 13-minutes when they lost Contepomi to a knee ligament injury and moments later Halfpenny knocked over his second penalty.
The full-back turned from point scorer to saver after a clinical counter-attack from the Pumas.
After turning over possession the ball was spread wide to Imhoff. The wing raced down the left and threaded a kick through. But despite winning the race Gonzalo Tiesi lost the ball under the tackle of Halfpenny.
Wales lost their own inside centre midway through the opening half as Roberts suffered a heavy bang to the head but Halfpenny fired the hosts into the lead with his third successful shot at goal.
Sanchez struck the uprights within minutes of the restart and totally miscued a second attempt minutes later as he slipped over on the greasy Millennium Stadium turf.
And Halfpenny punished the Pumas for their inaccuracy as he maintained his 100 per cent strike rate with another penalty but Sanchez made some amends with a second opportunist drop-goal.
The Pumas continued their resurgence and sparked the game into life with the opening try. Juan Manuel Leguizamon created the opening with a superb offload to Juan Martin Fernandez Lobbe, who released Imhoff.
And the Racing Metro star showed some dazzling footwork to round Halfpenny and score.
Sanchez slotted the conversion and Argentina were quickly back on the scoreboard with a second try. Again an offload did the damage and Camacho took full advantage with a superb finish in the corner.
Sanchez expertly converted from the touchline to hand his side a 23-12 advantage and leave Wales starring down the barrel.
Sanchez continued to keep the scoreboard ticking and put the pumas 14 points and out of reach. Wales rallied at the death but the visitors weathered the storm to claim a major scalp. – Sapa-AFP.