With a heaving crowd at Carrara Stadium roaring, Rio Olympic finalist Simbine blazed away after Blake botched his start, and crossed the line in 10.03 seconds, leading a South African one-two with team mate Henricho Bruintjies.
A stumbling Blake struggled for balance and by the time he regained it, the race was over, leaving him disappointed with the bronze and a time of 10.19.
The third fastest man of all time, Blake topped qualifying with a time of 10.06 and had been warned jokingly by Bolt not to come home without gold in his luggage.
“I was stumbling all the way,” the 28-year-old told reporters ruefully. “I just didn’t recover from it. It was a pretty easy race for me to win because I’ve been feeling good.
“It was just never (going) to happen today, I don’t know. I’m a bit disappointed because I’ve been feeling good, I’ve been running good.”
Bolt, who retired last year with eight Olympic golds including two 4×100 relay titles shared with Blake, tweeted his congratulations to his team mate and Simbine.
— Usain St. Leo Bolt (@usainbolt) April 9, 2018
“Well done @YohanBlake. Keep putting in the work. You know your journey,” the sprint great said.
The path to gold was made smoother for Simbine when England runner Adam Gemili, a 4×100m relay gold medallist at the London world championships, pulled out before the final with a thigh injury.
Simbine’s victory ended Jamaica’s domination of the Commonwealth 100m dating back to the 2006 Games in Melbourne.
“I wasn’t focused on (Blake). I was just focused on myself and making sure I get to the 50 metres as quick as I can because I know if I put that together the rest of my race will come together,” said the Pretoria 24-year-old.
“Being able to run in lane eight and lane nine with Henricho and placing first and second with him, it’s really amazing. And it’s a big thing for South Africa sprinting and South African sports.”
Jamaica was also denied in the women’s 100, with Trinidad and Tobago’s Michelle-Lee Ahye taking the gold in 11.14, holding off Blake’s team mate Christania Williams (11.21) and third-placed Gayon Evans.
It was a better night for world and Olympic 800m champion Caster Semenya, who kicked off her bid for a Commonwealth double with a comfortable win in the 1,500m heats in four minutes and 05.86 seconds.
The South Africa flag-bearer, who will run in the 800, qualified fastest for Tuesday’s final ahead of home runner Georgia Griffith (4:06.41) and Kenya’s Mary Kuria.
Even with the absence of Wayde van Niekerk and reigning champion Kirani James, the men’s 400m boasts quality and looks to be a battle between Botswana’s flamboyant Isaac Makwala and Grenada’s Rio Olympic finalist Bralon Taplin.
Makwala, who was barred from competing in the world championships’ 400 final in London last year over illness fears, qualified fastest for the final with a time of 45.00 seconds.
After crossing the line, the 31-year-old did two push-ups on the track and grinned at the TV camera.
New Zealand’s world champion Tomas Walsh threw 21.41 metres to take the shot put gold, going one better than his silver at Glasgow.
Stella Chesang fought off Kenya’s Stacy Ndiwa to take the 10,000m gold for Uganda and win her maiden Commonwealth medal.