There are reportedly huge plumes of black smoke and flames coming from the refinery.
While emergency response crews are on the scene, it is not clear how many units are there.
New Brunswick city resident Bob McVicar wrote on Facebook that it felt like a "bed-shaking explosion".
There were as many as 3,000 workers on the refinery Monday - but most of the facility was shut down for major maintenance, and almost all of the workers were contractors working on the turn-around.
Saint John Police also tweeted: "Police are now responding to an incident at the Irving refinery. Praying for the safety of all involved".
"We can confirm that a major incident has occurred at our Saint John refinery this morning", Irving said on Twitter.
Residents across the city reported feeling the effects of the explosion.
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The refinery is near several residential neighborhoods on Saint John's east side.
Irving Oil exports more than half of that to the United States, and the refinery is a critical source of fuel for the Northeast energy market, CNBC reported. "I heard a rumbling, roaring sound".
"We are actively assessing the situation at this time and will share more information when available", it said.
They looked outside the window and saw black smoke and flames exceeding the height of the stacks at the refinery.
He chose to drive by the refinery, and said he was nearby when he felt the vibrations of what he assumed must be a second explosion.
Saint John resident Michael Steeves says he was driving about a kilometre away when he noticed the fire and thick, black smoke. "At times we were letting that just safely extinguish itself", he said.