Hernandez came off the bench to score an 86th-minute winner as defending Copa champion Chile crashed to back-to-back defeats following last week's shock loss to Jamaica.
With the game seemingly petering out for a draw in the final warm-up fixture for both teams at Qualcomm Stadium in San Diego, Hernandez sprung the offside trap and headed powerfully past Cristopher Toselli as Mexico's unbeaten run extended to 19 matches.
Mexico recorded an eighth consecutive clean sheet in the process, with the Mexicans last tasting defeat in the 2015 edition of the Copa America.
Both Mexico and Chile made numerous changes to their starting XIs for the last pre-Copa clash before the tournament gets underway in the United States on Friday.
Juan Carlos Osorio rang the changes, with Nestor Araujo the only player to keep his place following Saturday's 1-0 win over Paraguay, as the likes of Hernandez and Rafael Marquez dropped out.
It was a similar story for Chile, with returning star midfielder Arturo Vidal part of three changes to the line-up, which included Alexis Sanchez, after last week's surprising 2-1 loss to Jamaica.
Chile made a lively start to proceedings, firing an early warning to Mexico after a swift counterattack saw Edson Puch's low shot flash just wide of the post in the second minute.
Mexico did enjoy some forays forward but Chile goalkeeper Toselli was largely untroubled as Puch was in the thick of the action again, striking the post approaching the half-hour mark.
Continuing to dictate play, Mena played an inch-perfect ball over Mexico's defense, picking out Puch at the back post and the 30-year-old LDU Quito winger hit the outside of the post, with Mexico fortunate to head into halftime on level terms.
The introduction of captain Andres Guardado gave Mexico fresh impetus in the second half, as the CONCACAF Gold Cup champion pegged Chile back in its own half.
Despite the improved display, the Mexicans never really threatened Toselli.
At the other end, Sanchez was played in on goal by Vidal but the Arsenal star's half-volley went just wide from a difficult angle after hour mark.
But Mexico had the final say after Hernandez - a replacement for Raul Jimenez - latched on to Miguel Layun's cross and made no mistake inside the penalty area as Chile was left to pick up the pieces with just one win in six games.