The 24-year-old from South Carolina, a bronze medallist in the 100m at the Paris Olympics last year, scorched home ahead of Tamari Davis, who was second in 11.03sec.
Thelma Davies was third in 11.14sec while Olympic 200m gold medallist Gabby Thomas – beaten by Jefferson-Wooden in Saturday’s 200m – was fourth.
Jefferson-Wooden’s time vaults her into elite company as one of the 10 fastest women over 100m in history.
“It means everything, I’ve been working so hard for this,” a delighted Jefferson-Wooden said afterwards.
“I’ve been learning so many new things about myself the way I go about training, the way I go about being disciplined, even when I’m not feeling my best, ” she added. “It’s just all coming together.”
Jefferson-Wooden’s time was only fractionally outside Julien Alfred’s winning time in the 100m at the Olympics last year, and suggests the American will be one of the favourites for gold at this year’s World Championships in Tokyo, provided she qualifies at next month’s US trials in Eugene.
In other races on Sunday, Britain’s Josh Kerr avenged his Olympic 1,500m defeat to Cole Hocker in a thrilling battle.
Hocker famously surged past Kerr to claim a shock victory in Paris last August at the Stade de France and take gold.
But on Sunday it was Kerr’s turn to produce a decisive finish, storming past Hocker in the final few metres to win in 3min 34.44sec. (AFP)
