The competitors took to the clay court following Rafael Nadal's victory over Juan Monaco at the Olympic Stadium, giving the Spaniards a 1-0 lead.
The news of Nadal's win seemed to have given his teammate the advantage as the 29-year-old got off to a positive start, edging the former US Open champion by four games to one.
Despite an initial push from Del Potro to make an impact for his Argentina team, Ferrer managed to see off the first set 6-2.
However, Del Potro used the fevered Argentinian support to fight back in the second, taking Ferrer to a tie-break in which he brushed aside the Spaniard 7-2.
Ferrer broke serve in the first game of the third before he held his own to establish a two-game lead.
Midway through the set the Spaniard began to slump as Del Potro clawed himself back into the match by levelling the set 3-3 with some explosive forehands.
By this point the momentum was firmly with the Argentinian, and a number of winners saw him find another break at 4-3 before he served out the set 6-3.
An early break in a tense fourth saw Ferrer take an early advantage, but the Argentine broke back to silence the Spanish crowd.
Ferrer soon found another break, and when Del Potro double faulted to hand his opponent the set 6-4, the match was taken into a final set.
The Spaniard struck first in the deciding set when he found a break of serve to establish a 3-1 lead. A tenacious Ferrer broke again as Del Potro was visibly waning.
The Argentine found an extra reserve of energy to breke back as Ferrer attempted to serve out the match, but the Spaniard would not be denied as he took the set 6-3 to claim the match.