The four-times Olympic and eight-times world champion, who has enjoyed most of her success in shorter sprints, coasted across the line in 50.60 seconds on the third morning of action at the iconic Bird's Nest stadium.
"It felt good. Good to get the first one under me. Just keep moving on," Felix told reporters.
"I just wanted to be able to control it (the race) early and try to get through as comfortable as possible."
With reigning Olympic champion Sanya Richards-Ross not taking part in China after failing to make it through the U.S. trials, Felix faces competition from 2008 Beijing Games winner Christine Ohuruogu (51.01) of Britain and Bahamian teenager Shaunae Miller (50.53), who both won their opening heats comfortably.
The crowd interest, though, concentrated on the long jump qualifiers where Wang Jianan (8.12 metres), Gao Xinglong (8.11) and Li Jinzhe (8.10) were all just shy of the 8.15m qualifying mark but easily made Tuesday's final in fourth, fifth and sixth.
The same could not be said for promising American Marquis Dendy, who could only muster a best of 7.78 metre effort after his final jump of well over eight metres was crossed off after a narrow foul he initially disputed.
South African Zarck Visser, who produced an 8.41m effort last month, also failed to make it through after the African champion could only register a 7.79m on Monday.
There were no such problems for Pan American Games champion Jeff Henderson of the United States, who nailed a solid 8.36m opening effort to lead the way ahead of the final on Tuesday evening.
"I did on my first try, it's great," he said.
Olympic champion Greg Rutherford also made it a comfortable morning, the Briton registering an 8.25m jump to finish just behind the American.
"The qualification showed me we are on the right way," he said. "I think we will need to show a big performance over 8.50 to fight for the gold. Jeff Henderson will attack it for sure."
Elsewhere, Olympic champion Jenn Suhr safely negotiated the qualifiers of the women's pole vault by clearing 4.55 metres at her second attempt, while Cuba's Denia Caballero (65.15 metres) pipped Olympic champion Sandra Perkovic (64.51) in the discus qualifiers.
(Writing by Patrick Johnston in Singapore; editing by Amlan Chakraborty)
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