Costa Rica picked up their first win of the 10-game campaign with a 2-0 victory over Jamaica in San Jose.
After three games, Panama, who have never qualified for a World Cup finals, lead on five points followed by Costa Rica, the U.S, and Honduras all on four points while winless Mexico have three points from their three draws.
A draw with Mexico and victory over the United States in home games, had given Honduras hopes of taking strong control of the group at supposed minnows Panama, but Julio Dely Valdes' determined team had other ideas.
A close range effort from Luis Tejada put Panama ahead in just the second minute of the game but Honduras roared back, Carlos Costly hitting the woodwork with a header in the 20thh minute.
Panama, who mix a high-speed attacking game with a physical approach, made sure of the three points when striker Blas Perez put the game beyond Honduras in the 75th minute, racing on to a through ball from substitute Nelson Barahona and firing home.
Costa Rica picked up their first win after Michael Umana opened the scoring with a side-foot finish having jinked into the box in the 22nd minute.
Jamaica enjoyed the better of the possession but Costa Rica substitute Diego Calvo grabbed the winner with a superb run, jinking past three defenders before curling the ball into the top corner.
The pressure was on Mexico at the Azteca Stadium against arch-rivals, the United States, and it showed as 'El Tri' failed to find the composed finishing touch to complete their dominant possession.
Mexico felt they should have had a penalty in the 76th minute when Javier Aquino went down under challenge from Maurice Edu but Guatemalan referee Walter Lopez waved away the appeals.
The hosts went close at the end with U.S. keeper Brad Guzan pulling off a superb save to keep out an Angel Reyna strike.
The result was just the second time that the United States have managed a point at the Azteca in a qualifier, following another goalless draw in 1997.
The U.S have never beaten Mexico at their national stadium in a qualifier.
After the final whistle fans, some of whom hurled objects at visiting U.S. supporters, chanted for the removal of coach Jose Manuel de La Torre.
The top three teams qualify automatically for next year's finals in Brazil with the fourth-placed team going into a two-legged playoff against New Zealand for a chance of securing a fourth berth from the region.