Fielding a team that is likely to be coach Bert van Marwijk's starting line-up in Ukraine and Poland, apart from the injured Joris Mathijsen, the Dutch took the Irish apart.
Van Persie opened the scoring after 11 minutes with a near-post header and added his second from the penalty spot after Wesley Sneijder had doubled the lead with a curling free-kick.
Afellay, who has been out for most of the season with a bad knee injury, finished off a fine move involving Van Persie and Arjen Robben to make it 4-0 by half-time.
The Dutch added a fifth through Afellay in the 51st minute before central defender Ron Vlaar completed the rout with a close-range header 12 minutes from time.
"I'm satisfied with the execution of our tactical plan today but the score means little to me as they were very poor opponents," Van Marwijk told reporters.
"My main concern is at left-back because Giovanni van Bronckhorst is now retired and his successor Erik Pieters is injured.
"Jetro Willems is young and has a lot to learn, Stijn Schaars has to get used to this position and Wilfred Bouma is another option," the coach added.
Netherlands travel to Poland on Monday and start their Euro campaign next Saturday against Denmark. Germany and Portugal are the other teams in Group B.
