Paraguay restored parity in the 17th minute when Jonathan Fabbro successfully converted the penalty conceded by Rodrigo Bran for a handball offence.
However, Alejandro Sabella's side regained their one-goal advantage at the Mario Kempes stadium in Cordoba in the 31st minute.
Real Madrid striker Gonzalo Higuain found himself with the ball at his feet following a Paraguay defensive mistake, and shot home after fending off Richard Ortiz.
Lionel Messi came close to making it 3-1 to the Argentines just minutes later when his free kick came off the Paraguay post.
The Barcelona forward was denied by the woodwork minutes into the second half when his delicate chip over Justo Villar hit the post.
Messi eventually scored in the 64th minute with a brilliant free kick from more than 30 metres to wrap a comfortable 3-1 win for the Albiceleste.
The win over Paraguay means that Argentina are currently top of the CONMEBOL standings with 13 points from six matches, just one point ahead of both Chile and Ecuador.