Richardson lost her place at the Tokyo Olympics after a positive cannabis test and failed to qualify for last year's worlds but would not be denied this time around, beating Brittany Brown by eight hundredths of a second.
Tamari Davis took third in 10.99.
The fan-favourite Richardson got off to a lacklustre start but kept her poise, surging into the lead after the 60-metres mark and bounding into the stands to hug her supporters immediately after crossing the line in Eugene, Oregon.
"I'm ready mentally, physically and emotionally," she said in televised remarks. "And I'm here to say: I'm not back - I'm better."
She set a new world lead of 10.71 on Thursday, only to have Jamaican Shericka Jackson eclipse that effort on Friday at home in an eye-popping 10.65, setting up a tantalizing showdown for the worlds in Budapest, Hungary, that begin Aug. 19.
On the men's side, Charleston exploded off the blocks in a flawless performance to hold off the 2019 world champion Christian Coleman at the last moment by one hundredth of a second.
"I'm just honoured, privileged to be here," said Charleston, who had failed to get past the semi-finals on the same Hayward Field track only a year ago.
Twice 200m world champion Noah Lyles (10.00) finished third despite recovering from COVID-19 only days earlier to achieve his goal of booking a spot on the world stage in the shorter sprint.
"This is probably the hardest team I've ever had to make in my life," said Lyles, who won the Paris Diamond League last month but was unable to train for a week leading up to Eugene because of his illness.
"I had to keep believing that I was just going to keep going. I had that dream that I was going to make that (sprint) double... I didn't feel like I was going to really be part of the team unless I made the team in the 100 this year."
'A GOOD SPOT'
Hurdle queen Sydney McLaughlin's foray into the 400m flat continued without issue as she glided into the final round with a 49.60 win on Friday.
"Just getting used to the rhythm," McLaughlin said in televised remarks. "The goal is always to make the team and then you go from there so (I'm) just excited, feel like I'm in a good spot."
Olympic silver medallist Kendra Harrison cruised to the fastest time across the 100m hurdles opening heats in 12.50, advancing to Saturday's semi-final along with 2019 world champion Nia Ali.
Twice world silver medallist Rai Benjamin rolled through the men's 400m hurdles opening round with the fastest time of 49.05 while Dalilah Muhammad, the 2019 world champion, advanced on the women's side in 54.56.
World bronze medallist Anna Hall won the heptathlon and Harrison Williams punched his ticket to Budapest in the Decathlon.
In the field events, world indoor bronze medallist Donald Scott won the men's triple jump with 17.22 metres while Will Claye punched his ticket to his seventh worlds as he finished second with 16.98.
Vashti Cunningham, who took the third spot on the podium in Doha, won the women's high jump with 1.91 metres.
The top three finishers across all events in Eugene who meet certain qualifying standards, as well as reigning global title-holders, will advance to the world championships.
The U.S. championships continue on Saturday.
