The result was only the second time the US have earned a point from a qualifier at the Azteca and the gutsy display with an injury-hit squad took the US to four points from their three games.
Panama top the standings on five points from three games with Costa Rica second in the table, ahead of the US on goal difference.
Mexico had the better of the possession and the chances but were unable to find a way past a well-organised and determined US back line, although they will be furious they were not awarded a penalty in the second half.
Javier Aquino went down under challenge from Maurice Edu in the 76th minute but Guatemalan referee Walter Lopez waved away the appeals.
The home side began brightly and clearly targeted stand-in left back DaMarcus Beasley with right-winger Aquino being joined by Giovani Dos Santos on the flank to cause early trouble for Juergen Klinsmann's side.
Aquino was brought down by Beasley in the eighth minute, earning the US defender a yellow card to further add to his difficulties.
Dos Santos whipped the resulting free-kick across the face of goal but Mexico clearly felt an early strike was within their grasp.
Dos Santos's volley in the 20th minute straight at US keeper Brad Guzan was, however, the only real threat on goal that Mexico produced from their early pressure.
After their shaky start, the US, gradually grew into the game, slowing down the pace and looking to hit Mexico on the counter attack.
Midfielder Michael Bradley led a couple of smart breaks but the US were content to reach halftime with the game still goalless.
Mexico began the second half brightly again with Aquino's cross-shot clipping the top of the bar and this time their early promise was turned into sustained pressure.
The inexperienced US central defensive pairing of Matt Besler and Omar Gonazalez had impressive displays, keeping Mexico's main strike threat Javier Hernandez quiet and making several timely interceptions.
Jesus Zavala went close with a deflected shot in the 69th minute while the US made changes with Eddie Johnson replacing Jozy Altidore at centre-forward and then Brad Davis taking over from Herculez Gomez on the left flank.
Mexico then had their penalty claim rejected with 14 minutes remaining and deep into injury time, Angel Reyna forced a great save out of Guzan with a fierce drive but the US survived, leaving the crowd of 95,000 frustrated at the final whistle.
The third straight draw leaves Mexico in fifth place in the six-team group, a point behind Honduras with Jamaica propping up the table on two points.
The top three teams qualify automatically for next year's finals in Brazil with the fourth-placed team going into a two-legged play-off New Zealand for a chance of securing a fourth berth from the region.