An early goal from Luis Tejada and a late one from Blas Perez sandwiched an extended, but ultimately fruitless, push from the Catrachos, who couldn't find a way past a resolute Panamanian back line stewarded by stand-in goalkeeper Luis Mejia.
The host got off to a dream start in just the second minute, when Leonel Parris got into the box alone on the right side. His pinpoint cross provided Tejada with the easiest of finishes, staking Panama to the early lead.
Honduras immediately took the initiative, and nearly tied through Carlo Costly - the hero of last week's draw with Mexico in San Pedro Sula - who rose to beat Mejia with a powerful header which rang the crossbar in the 20th minute.
Panama went to the half with the minimum advantage. Just minutes into the second stanza, however, the Hondurans had another golden opportunity to tie through Costly, but his shot was stopped by Mejia after the forward got into the box alone.
In the 75th minute, Panama finally made their guests pay for the missed chances, when second half sub Nelson Barahona picked out Blas Perez with a long pass from midfield. The 32-year-old forward took a touch and then slammed a right footed shot past goalkeeper Noel Valladares.
The victory left Panama atop the Hexagonal table with five points after three matches, one better than Honduras. The Canaleros will next host Mexico on June 7, while Honduras visits Costa Rica that same day.