McLeod, 23, led from start to finish to take the title in 13.04 seconds from defending champion Sergey Shubenkov with Balazs Baji.
However, world record holder Aries Merritt's dream of winning at least a medal two years after a kidney transplant were dashed as the American 2012 Olympic champion finished fifth.
McLeod, 23, led from start to finish to take the title in 13.04 seconds from defending champion Sergey Shubenkov with Balazs Baji of Hungary taking a surprise bronze.
"It's crazy, it's my moment," said McLeod.
"I had to win tonight as my mother (Arnella Knight-Morris) was watching in the stands."
"I dedicate this win to my mother."
McLeod provided Jamaica with a much needed boost after both Bolt and women's double Olympic sprint champion Elaine Thompson failed to bring home gold in the 100m.
"I really wanted to come out here and keep the Jamaican flag high," said McLeod.
"Usain Bolt he's still legendary, this is also for you! His legacy to Jamaican athletics he deserves such a tribute!"
McLeod added: "This one is special, honestly. There was a lot of pressure coming in but I channelled it positively."
"It's totally different to last year where we had Usain and Elaine winning, which I used to propel me. I didn't have that this time so I really wanted to come out and shine my own light."
McLeod dominated the race leaving the others to fight it out for the minor medals with Merritt in contention until the final hurdle.
However, he weakened and Russian Shubenkov, who was running as an Authorised Neutral Athlete because of his country's ban over a massive doping scandal, burst through to take second with 2016 European silver medallist Baji edging Frenchman Garfield Darien for the third spot on the podium.
"I'm so frustrated," said Shubenkov. "I struggled over the last few hurdles."
"The Jamaican is just too fast. I'm just happy to be competing at a world champs and get a world medal. Last year was a disaster and not just because of the Russian ban (on competing at the Olympics) so I'm happy to be back winning a world medal."
"To be honest it doesn't matter the colour of the vest I am wearing, it is more important that I gave pleasure to the people in my country who were watching."
Merritt said it felt "great to be back in London where I won Olympic gold".
"The crowd greeted me very warmly. Of course, I am not happy to be in lane nine but just being in the stadium is enough for me," he said.
"I am not even meant to be running, so I'm more happy to be here than not be here. I am back on the world stage, that's the main thing."
"It's definitely possible for me to medal in the future. Everyone in the hurdling game is hurdling well."
"Since I broke the world record it's really transformed. There are a lot of new people and new talent, and that's fine. I'm just happy still to be part of it."