In cool conditions in Australia's Gold Coast, South Africa's Simbine stormed up lane seven to win his first major title in 10.03sec, the second fastest time this year.Blake, the fastest man into the final in 10.06, stumbled out of the blocks and dipped for bronze in a disappointing 10.19, behind South African silver-medallist Henricho Bruintjies' 10.17. Blake was 0.02 further back to get bronze after a photo finish with Nigeria's Seye Ogunlewe.
Trinidad and Tobago's Michelle-Lee Ahye won the women's 100m in 11.14, ahead of Christania Williams in 11.21 and her fellow Jamaican Gayon Evans, who clocked 11.22. So the pressure on Blake intensified.
Alongside the likes of Canada's Andre de Grasse and Christian Coleman, of the United States, Simbine represents the future of global sprinting and he took a significant scalp on the way to victory in the Gold Coast by beating Yohan Blake, the second fastest man in history.
'I was stumbling all the way and I didn't recover from it, ' Blake said after the race.
"I'm disappointed because I've been feeling good". I was supposed to take this (race) very easily because I was ready and feeling good. I've never had a 50m Commonwealth title.
Blake hopes to claim the title as a stepping stone to restoring Jamaica's primacy in the event following last year's retirement of Usain Bolt.
"Well done @YohanBlake. Keep putting in the work".
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"I wasn't focused on him [Blake], I was focused on myself and making sure I got out fast and that I got to the 50m as quick as I could", he said.
Blake got stronger as the race progressed, but he could not get anywhere near Simbine while Bruintjies held on for the biggest result of his career.
"Being able to run in lane eight and lane nine with Henricho and placing first and second with him, it's really wonderful".
"I think everybody is celebrating and everybody believes sprinting in South Africa has been a long time coming and we can have a South African on the podium and now we can have two on the podium".
He was a class apart as he galloped over the finish line in 10.03. England's Asha Philip was fourth in a repeat of her finish in Glasgow four years ago.
Yohan Blake wants to add a Commonwealth Games title to his collection from the Olympics and world championships. Although, it came in the absence of the top Jamaican, Elaine Thompson, who won the Olympic 100-200 double in 2016 but is only running the 200 on the Gold Coast.
"I'm not anxious", said Blake of Bolt's likely disappointment, in what was the first major championship since the sprint legend called time on his career. In other high-profile events, Olympic and world 800-meter champion Caster Semenya started her quest for a games double with a commanding win in the heats of the 1,500.