Felix, 33, racing in her first meeting for more than a year after taking time off to give birth to her daughter, finished sixth in the 400m final at Drake Stadium.
Although Felix could still travel to Doha as part of the USA's 4x400m relay squad, it will be the first time she has not entered an individual event at a major championships, ending a sequence of appearances that stretches all the way back to 2003.
"I just didn't feel great," Felix said afterwards.
"I knew that it was a less than ideal situation for me."
Felix, however, said she was encouraged by her performances in Iowa as she looks towards the 2020 Olympics.
"I am grateful more than anything," she said. "It would be crazy for me to say that I was disappointed. I have my health, I have my family and I couldn't ask for anymore than that."
Asked if she would take a place on the US relay squad for Doha if it was available, Felix said form and fitness would influence her decision.
"If I feel like I'm in good form to be able to help the team, then yes," she said. "If not I'll be a cheerleader."
The upset of the day came in the 400m, where rising star Michael Norman was beaten for gold by the powerful Kerley.
Norman has lit up athletics in his first professional season this year with a world leading 43.45sec.
But he was unable to overhaul Kerley down the stretch as the 24-year-old Texan muscled his way to the line in a personal best of 43.64sec, making him the seventh fastest 400m runner of all time.
In the women's 100m hurdles, world record holder Keni Harrison produced a flawless display to take gold in 12.44 sec, with Nia Ali second in 12.55sec and Olympic champion Brianna McNeal third in 12.61 sec.
There was another dominant victory in the men's 400m hurdles where the 22-year-old Rai Benjamin registered an emphatic win, surging clear of the field to win by around 10 meters.
Benjamin's time of 47.21sec was the third fastest time of 2019. He already owned the second-quickest of the year of 47.16 and only Norway's Karsten Warholm has run quicker, with a 47.12.
The outstanding field event performance of the day came in the men's pole vault, where world champion Sam Kendricks soared to a world leading jump of 6.06m, a new American record. Only two men, Ukrainian legend Sergey Bubka and France's Renaud Lavillenie, have ever jumped higher.
The popular Kendricks was buried under a pile of his fellow competitors after clearing the height, which was also a new personal best.
"As I was falling I was thinking 'They are going to come tackle me'," Kendricks said of his fellow competitors. "We're a pretty tight-knit group all around the world in the pole vault."
Elsewhere Saturday, Christian Coleman and Noah Lyles remained on course for a 200m showdown after sailing through their heats.
Coleman, who romped to an emphatic victory in the 100m final on Friday, was always in control of his heat, easing up well before the finish to qualify with a time of 20.70sec.
"My body feels really good right now," Coleman said.
Lyles, the fastest man in the world this year over 200m with a season-leading 19.50sec, was similarly unruffled in his heat, sauntering home in 20.65sec.
The 22-year-old from Florida sported a new silver-gray hair colour for his race, a tribute to a character in Japanese manga series Dragon Ball.
"It was pretty easy," Lyles said afterwards. "I just wanted to conserve as much energy as possible. It felt good to finally get out there. I've been here since Monday. I'm ready to run."