Almost 2,000 people will lose their jobs when Michelin and JTI Gallaher close within the next two years.
Liam Neeson, who is originally from Ballymena, has lent his voice to the campaign.
A message from the Hollywood actor was played to the crowd on a big screen on Saturday.
He told them "this is the start of the fight back".
Other speakers at the event asked for politicians at Stormont to take note that they want manufacturing jobs brought back to Ballymena.
One 17-year-old told the crowd she had no option but to leave her home town in search of work.
"Stormont aren't recognising us as a town worthy of investment," Shealyn Caulfield said.
"They need to get off their backsides and put some energy and put some hope and life back into a town that we love so much.
"We look towards our politicians and our leaders to care for us, but all they're doing right now is covering their tracks from the past and fighting about it and they're so engrossed in it."
The rally was organised by the Unite union.
The union's Irish regional secretary Jimmy Kelly said thousands of well-paid and well-organised jobs were being lost and that a community spirit had developed within the workforce at the two factories.
"What we didn't want to do was this day next year talk about how terrible it is," he said.
"Young activists here in Ballymena wanted to do something, wanted to fight back, wanted to declare to politicians that they've got to get the investment and build a future here."
Last November, it was announced that the Michelin tyre factory in the town would close in 2018 with the loss of 860 jobs.
It was the second major jobs blow to the town in just over a year.
In October 2014, cigarette maker JTI Gallaher announced it would be shutting its plant in the town with the loss of 800 jobs.
Redundancies there are expected to begin in May 2016 and the factory will shut down completely in 2017.
Hundreds of people have attended a rally in Ballymena calling for investment to bring new jobs to the town.