"Following Paraguay's elimination from the Copa America Centenario, Ramon Diaz has confirmed his resignation as national team coach with immediate effect," the federation said in a statement yesterday.
Paraguay were dumped out of the tournament after collecting just one point from three games, a draw against Costa Rica.
Their exit was confirmed on Saturday after they lost a must-win game to the United States, who advanced from Group A along with Colombia.
Diaz, a former Argentina international, had taken over as Paraguay coach in 2014, successfully guiding the team to the semi-finals of the competition last year in Chile.