A local woman, 25, has been arrested on suspicion of DUI after her car hit the crowd in Stillwater.
Witnesses described dozens of bodies being flung into the air.
Police said it was one of the worst accidents they had seen in 30 years.
The initial death toll was three, but a two-year-old boy died later from his injuries.
Five children and three adults remain in hospital, some in critical condition, officials say.
The car crash happened as the crowds were watching a homecoming parade – a traditional event welcoming back Oklahoma State University (OSU) alumni.
The vehicle is reported to have hit a stationary police motorbike – which had no rider at the time – before plunging into spectators at the homecoming parade.
Stillwater Mayor Gina Noble said that the incident had left people in the town heartbroken, while OSU President Burns Hargis said that what was supposed to be “a wholesome, happy event” had been besmirched by “a terrible tragedy”.
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