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.
The Pumas UNAM forward only had to wait two minutes into his first start for Mexico to make up for that with his maiden goal.
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.
It could have been 2-0 three minutes later but Herrera was correctly penalised for standing too close to a free-kick for Paraguay, which he intercepted, before slotting the ball in the bottom corner.
With Mexico pressing high and causing their opponents problems, Paraguay attempted to gain the ascendency through their physicality with Richard Ortiz going into the book in the ninth minute.
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.
But in a match of few genuine chances, Paraguay should have equalised just before half-time when Ortiz was left unmarked at a corner but his header crashed off the crossbar.
The second half continued the theme of the first with a lack of quality in the forward areas and regular free-kicks.
The match ended with 43 fouls and seven yellow cards, as Paraguay coach Ramon Diaz was forced to wait for his maiden win in charge of the South Americans, after a scoreless draw at Costa Rica last week.
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