First-half goals from Panama pair Blas Perez and Luis Tejada condemned visitors Costa Rica to their first defeat in eight matches.
Panama drew first blood through Perez in the 17th minute before Tejada doubled the home side's lead eight minutes later at Estadio Rommel Fernandez Gutierrez in Panama City.
Substitute Alvaro Saborio converted a 67th-minute penalty to offer Costa Rica some hope but Panama held on for their second win over the international period, having edged Trinidad and Tobago 1-0 on Friday.
Perez - joint-top scorer in the MLS this season with three goals in as many games - gave Panama a well deserved lead after 17 minutes.
The FC Dallas star flicked the ball up and volleyed it past Costa Rica goalkeeper Esteban Alvarado - momentarily moving level with Tejada as Panama's all-time leading scorer with 37 goals.
However, Tejada - who plies his trade with Juan Aurich - edged clear again in the all-time standings eight minutes later, reacting quickest to side-foot a rebound from close range.
Costa Rica pulled a goal back midway through the second half following a foul on Marco Urena.
Harold Cummings was adjudged to have brought down the striker and Saborio - Costa Rica's third-highest scorer - made no mistake from the spot, sending Jaime Penedo the wrong way.