Pearson was considered the main challenger to world record holder Kendra Harrison heading into the event, and with the American putting in a messy performance it was the Australian who took her second world title in a time of 12.59 seconds, adding to the one she won in Daegu back in 2011.
Pearson broke her wrist in 2015 and missed the 2016 Olympic Games with achilles and hamstring injuries.
Manning won in 12.71, while the Williams, who had the second fastest time following the fist round in the morning session, crossed the finish line in a disappointing 13.14.
"I've worked so hard, I don't know what has just happened out there".
"I don't know if it was surprise or what", said Pearson of her exuberant celebration.
"I love this stadium, I love the people and I'm so happy to be back here doing the same thing again".
The 30-year-old timed 12.59 seconds to take the crown ahead of 2008 Olympic champion Dawn Harper-Nelson (12.63sec) with Germany's Pamela Dutkiewicz, a surprise third in 12.72.
"I can not believe it, it's insane", said Dutkiewicz. I am glad I caught this moment of complete flow, of complete concentration.
Harrison - who was the 1/6 on favourite for the title and had not been beaten in a race since the US Olympic trials past year - at least made it unlike Jamaica's defending champion Danielle Williams who flopped to finish fifth in her semi.
"They're the ones I have to thank tonight because I don't think I would be here without them".
Favourite Kendra Harrison, who set the world record in the London Stadium previous year having missed out on Olympic selection, clattered too many barriers as she did in the semis and finished fourth in 12.74.
Once Pearson arrived at the pre-championships training camp in Tonbridge she handed responsibility for the final stage of her buildup to Australian head coach Craig Hilliard and team coach Matt Beckenham.
Harrison, who was disqualified in the semis two years ago, had been unbeaten in 23 races until the semi-final in London on Friday but her wait for a championship medal goes on.
Megan Simmonds, who was second behind Williams at the Jamaican Championships, could only manage fourth place in the first heat.