Jesus Corona and Jurgen Damm came off the bench to maintain Mexico's winning start to World Cup qualifying, but a serious injury to Honduras midfielder Luis Garrido overshadowed the 2-0 victory.
Garrido looks certain to have broken his leg after an unfortunate coming together with Javier Aquino at the end of the first half, with a lengthy lay-off appearing extremely likely.
The freak accident proved to be the only talking point of a dull opening period, with neither goalkeeper truly challenged until Javier Hernandez forced Noel Valladares into a one-handed save shortly after the interval.
But substitute Corona kick-started the Mexican challenge in the 67th minute in San Pedro Sula, before Damm - another replacement - made sure of the win by tucking home from a tight angle.
The result sees Mexico follow up their 3-0 CONCACAF Group A victory over El Salvador in the opening round of fixtures, while Honduras remain bottom as they failed to bounce back from their reverse in Canada.
Still smarting from Friday's defeat, Honduras looked determined not to suffer similar disappointment in front of their own fans, and Mario Martinez's full-blooded challenge on Oswaldo Alanis in the opening two minutes demonstrated that desire.
Mexico struggled to impose themselves on the fixture in the early stages, with Honduras enjoying the lion's share of possession, and Rubilio Castillo had a half-hearted claim for a penalty waved away by the referee.
Replays suggested very little contact, but the incident should have served as a warning signal to Mexico, who offered little going forward throughout the opening period.
However, it was the niggling challenges that came to characterise a scrappy first half in which Garrido was carried off on a stretcher following a horror collision with Aquino.
Still stumbling following a challenge from Wilmer Crisanto, Aquino fell into the leg of Garrido, appearing to snap it in half.
That incident contributed to six minutes of added time at the end of the first half, but it was not until early in the second that either side went close.
Having received the ball in the box, Hernandez drew a superb diving save from Valladares, with Raul Jimenez unable to turn in the rebound from close range.
But the breakthrough finally came when Corona, on for Aquino four minutes earlier, improvised well to control the ball at the edge of the box and unleashed a venomous drive into the bottom left-hand corner.
Damm then wrapped up the victory two minutes after coming on, drifting in from the right after shaking off a challenge and side-footed home.