The performance, the fastest in the half-lap event in 14 years, set Felix up for a London showdown with Jamaican Olympic Veronica Campbell-Brown, who has defeated the American in the last two Games.
"I was thrilled with my race," Felix told said. !I feel like everything came together. I felt like I executed today and ran a great curve, which is something I've been working on.!
World and trials 100 metres champion Carmelita Jeter finished almost a half second behind Felix in 22.11 seconds.
Sanya Richards-Ross, the trials' 400m winner, also made the US team in a second event by finishing third in 22.22.
But Felix's training partner Jeneba Tarmoh missed a spot on the team in the 200 with a fifth place finish in 22.35.
The sparkling race came minutes after world indoor hurdles champion Aries Merritt had cruised to the year"s fastest 110 metres high hurdles in a lifetime best 12.93 seconds despite wet conditions.
"I had a great start and I'm a build hurdler, I get faster as I go. I fulfilled my dream today," said Merritt, who became the 14th hurdler to break the 13-second barrier but remains behind the world record of 12.87 set by Cuban rival Dayron Robles.
World champion Jason Richardson, who had broken 13 seconds for the first time in the semi-finals, was second in 12.98 while Jeff Porter claimed a surprising third in 13.08.
Ailing American record holder and Olympic medallist David Oliver missed out on a trip to London when he finished fifth, running 13.17.
"I just didn't get it done," said a hobbling Oliver.
Felix clearly did, though, with her stirring run through the bend and down the home stretch.
"It was fantastic," coach Bob Kersee told Reuters after watching Felix cruise home in her bright neon compression leg sleeves.
"To run 21.69 in these conditions shows what kind of world class athlete she is. At 80 metres (into the race) she was digging."
Felix, Tarmoh and Kersee said no decision had been made on how the two would decide their controversial third-place tie in the 100 metres.
Under newly adopted tie-breaking procedures, the athletes have a choice of a coin flip or runoff if one of them does not give up her 100 metres spot.
"I don"t think the world would accept a coin flip at this point," Kersee said. "The other two options are up to them."
USA Track & Field officials have told Kersee and the athletes any runoff should take place on Sunday, the final day of the trials.
World triple jump champion Christian Taylor showed he was ready to claim gold in London with the best mark in the world this season, 17.63 metres.
Global indoor winner Will Claye also looked like a medal contender as he bounded 17.55 metres.
Olympic silver medallist Hyleas Fountain dominated the heptathlon with 6,419 points. Sharon Day and Chantae McMillan also booked trips to London.
In the women"s high jump, indoor champion Chaunte Lowe did not allow the rain to slow her.
Lowe cleared an impressive 2.01 metres to win on misses over collegian Brigetta Barrett, who mastered the same height.
The 36-year-old Amy Acuff made her fifth US Olympic team by coming out of a two-year retirement to place third at 1.95 metres.
"Deep down I felt like I had unfinished business so I had to come back," said Acuff.