The European Champion clocked 9.97 seconds at Hayward Field and finished second to favorite Fred Kerley in his run.
Hughes, who only reached last year’s Olympic final after a false start, expects drama on Saturday after seven sprinters ran under 10 seconds in the heats.
“It’s a really fast track. It’s really exciting. What made me happy was when the F18s flew over the stadium, that really gave me gas,” said the 27-year-old, who qualified fifth fastest.
“Kerley ran 9.79 seconds, I think it’s the fastest ever in the heats. There were some good names, but I don’t focus on names, I don’t focus on times. Leave what happened in the season behind. What counts here counts.
“I said during the stages that I’m fine, I just have to trust myself, trust my speed. My trainer told me: “Don’t worry about the start, just focus on what needs to be done, execute it and you’ll be fine.”
“I didn’t panic. Su (Bingtain) is a great starter, the other guys are great starters and I’ve never been the best starter in the world.”
Prescod ran 10.15 seconds and finished fourth in heat four but failed to secure a qualifying spot in a surprise elimination.
Africa’s fastest man Ferdinand Omanyala won his race against the clock, starting in heat seven. He had visa issues prior to his trip to Oregon and landed just hours before his race and qualified third.
Defending champion Christian Coleman of the USA, returning after being suspended due to a lack of drug tests, ran 10.08 seconds as he slowed down the line.
in pole vault, Holly Bradshaw retired after an unusual incident during warm-up, saw her stick snap and she landed unhappily on her neck.
She was helped off the mat and decided to quit after experiencing some discomfort.
Laura Muir made it to the 1500m semifinals with a controlled race on Saturday, finishing second behind Hirut Meshesha of Ethiopia.
Muir sat at the back of the field for the first two laps before moving, setting a four minute and 07.53 second time. Katie Snowden and Melissa Courtney-Bryant got stuck.
Amy Strickler threw 17.40 m and Sophie McKinna 17.21 m, but they did not reach the shot put final.
Earlier, Great Britain missed out on a place in the 4x400m mixed relay final.
Joe Brier, Zoey Clark, Alex Haydock-Wilson and Laviai Nielsen clocked three minutes and 14.75 seconds, finishing sixth and ninth fastest in their heat.
The Dominican Republic won Friday night’s final – the first gold of the championship – ahead of the Netherlands and the USA.
Nick Miller qualified for Saturday’s hammer final after finishing ninth in Pool A and throwing 77.13m, but Joel Clarke-Khan failed to complete the high jump after clearing just 2.21m.