Elite athletes were joined by those running for charity as thousands more lined the streets to cheer them on amid tight security.
After a minute's silence before the start of the race, runners sang Oasis anthem "Don't look back in anger," a moment described as "intensely poignant" by Rishi Makwana.
"Determination mixed with absolute unity -- very powerful," is how Makwana described the event on his Instagram when asked by CNN.
"This run holds personal significance for me so that made it all the more powerful. The city and its people are incredible."
The run included both a half-marathon and 10-kilometer course.
Thousands came wearing yellow ribbons, others sported the famous Manchester bee tattoo
, while there were hundreds of messages of resilience.
There was also huge applause from the runners and watching crowds for the emergency services, who have worked tirelessly throughout the week.
Sara Campbell, resplendent in yellow and with a ribbon in her hair, said Monday's events had made her even more determined to complete the half-marathon course.
"It made me want to do it more," she told CNN.
"I wanted to come together and show that we won't be defeated."
Manchester Mayor Andy Burnham, who ran in the event, told reporters it had been a "difficult decision" to let the race go ahead.
"We took advice from the police and the security services," he said.
"But the consensus always was that if we were to cancel that's a victory for those who seek to disrupt our way of life and I don't think we were prepared to give them that victory."