The fine - the largest in OSHA's history - comes after a 6-month inspection revealed hundreds of violations of a 2005 agreement to repair hazards at the refinery.
OSHA also says the company committed hundreds of new violations by failing to follow industry controls on pressure relief safety systems and other precautions.
A BP spokesman says the company believed it was in "full compliance" with the settlement agreement and will work with government officials to resolve the issue.
"We are disappointed that OSHA took this action in advance of the full consideration of the Review Commission," the London-based company said in an emailed statement, referring to an ongoing separate inquiry by a body separate to OSHA.
"While we strongly disagree with their conclusions, we will continue to work with the agency to resolve our differences," the company added.
BP said its efforts to improve process safety performance "have been among the most strenuous and comprehensive that the refining industry has ever seen."
The refinery - the third largest refinery in the U.S. - extends over nearly two square miles on the outskirts of Galveston.
On March 23, 2005, BP employees and contract workers began an especially dangerous procedure: re-starting a unit that had been down for repairs. They began to fill a tower with gasoline. The tower overflowed, and the excess gas flowed into a back-up unit, which then also overflowed and sent a geyser of gasoline into the air.
The plume of gas formed a massive vapor cloud on the ground, and an idling truck likely ignited the fumes.
The blast pulverized several office trailers full of workers parked nearby.