The American won his heat in 4 minutes, 7.82 seconds - 44-hundredths of a second better than his gold medal-winning time four years ago in Athens. Phelps was under his world-record pace after 150 meters of the four-stroke race, but eased off to save something for Sunday morning's final.
Laszlo Cseh of Hungary, the bronze medalist in Athens, was second-fastest in 4:09.26. Luca Marin of Italy was third in 4:10.22, and American Ryan Lochte qualified fourth in 4:10.33.
Phelps walked onto the deck of the Water Cube for his first of five individual events in front of 17,000 fans, who were mostly quiet.
He wiped down the starting block in lane four with a white towel as Lochte churned through the final meters of his heat. Phelps first stretched his right leg on the block, then his left before removing his ear buds and getting ready to race.
The crowd came alive for the women's 100 butterfly, where China sent out its first two swimmers of the competition. Zhou Yafei tied American Christine Magnuson for second-quickest in 57.70 seconds. Leading the way was Jess Schipper of Australia in 57.58.
The other Chinese, Xu Yanwei, was 32nd and didn't advance to the semifinals. Neither did Otylia Jedrzejczak of Poland, the silver medalist in Athens who finished four-hundredths of a second out of the 16th and last spot.
American Elaine Breeden moved on in sixth place, as did Aussie Libby Trickett, who was 12th.