Andres Guardado also scored and Alfredo Talavera was solid in his debut in goal for Mexico, who delivered a strong performance in their first match since last year's disappointing exit in the round of 16 at the World Cup.
The match was just what new coach Jose Manuel de la Torre was looking for as his team prepares for the CONCACAF Gold Cup starting in June, while Paraguay are gearing up for the Copa America.
Mexico, who play Venezuela down the California coast in San Diego on Tuesday, took charge early and didn't back off.
Hernandez, who has 10 goals for English Premiership power Manchester United this season, headed in a ball from Pablo Barrera in the sixth minute to open the scoring, his effort eluding Paraguay keeper Justo Villar.
After Guardado made it 2-0 in the 29th minute, the 22-year-old Hernandez added his second goal in the 34th with another shot from in front of the goal.
When he exited in the 65th minute, Hernandez received a rousing ovation from the pro-Mexico crowd.
Fans who camped out late Friday transformed the Oakland Coliseum -- home of the NFL's Raiders and baseball's Oakland Athletics -- into a fiesta of green and red, with attendance announced at 48,110.
Talavera, one of three goalkeepers that de la Torre is considering for the starter's spot, almost had a clean sheet.
But Cristiano Riveros scored in the 87th minute for Paraguay, getting to a corner kick and slotting it between Talavera and the post.
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