Nicaragua scored first, but Panama answered quickly to seize three points in Group B, which saw the United States and Martinique playing later Wednesday at the same venue.
After a scoreless first half, Nicaragua seized the lead in the 49th minute when Carlos Chavarria hit a right-footed shot from outside the box into the top left corner of the goal.
Just a minute later, Panama's Ismael Diaz knotted the score with a left-footed effort from the center of the area.
Panama seized the lead in the 57th with a goal from Gabriel Torres in the center of the area.
In the second game of the day's double-header at Raymond James Stadium, the United States were aiming to bounce back from a disappointing 1-1 draw with Panama in their opening match in the regional championship for North and Central America and the Caribbean.