The 26-year-old striker volleyed Juan Carlos Medina's free-kick home at the back post in just the third minute at Arrowhead Stadium, and while Mexico had the better of the chances for the rest of the match, they had to settle for successive one-goal wins.
Mexico's blistering start - Herrera had a second goal ruled out in the sixth minute - saw Paraguay attempt to shut the match down by outmuscling their opponents, and the game at times descended into simply a string of fouls and dangerous tackles.
Miguel Herrera's Mexican side have three more friendlies before they kick off their Copa America campaign against Bolivia in June.
Herrera had made his international debut in the final seconds of Mexico's 1-0 win over Ecuador on Saturday but did not touch the ball.
Herrera stood in an offside position as Medina prepared to take a set-piece from the left and as the striker moved back onside, Paraguay's defence did not pick him up.
Paraguay goalkeeper Justo Villar stayed on his line and Herrera toe-poked Medina's cross into the top corner of the net.
Herrera was one of 10 changes to Mexico's starting line-up from the victory against Ecuador with only defender Diego Reyes keeping his spot.
Villar picked up an injury and was replaced by Antony Silva in Paraguay's goal on the half-hour mark, and Raul Jimenez tested the new gloveman with a long-range shot four minutes later.
