Fast-moving flames and thick smoke were seen shooting out of the roof and windows of the warehouse in the 2000 block of West Lugonia Avenue about 5:30 a.m.
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The 10 Freeway near Mountain View Avenue was shut down as fire crews poured streams of water on the inferno, which appeared to engulf almost all of the sprawling structure.
"I just heard people yelling that there was a fire," said Aquaria Canteen, an employee at the third-party fulfillment center, which helps facilitate the deliver of large items such as furniture and televisions. "And I as all the way at the other end of the warehouse, at the last door. I turned around and you could see smoke and flames."
Several Amazon trucks burned on the loading docks of the building, whose square footage is equal to about three football fields. A spokesman for the e-commerce company refuted initial reports that the building was owned by Amazon.
Firefighters from multiple agencies across San Bernardino County responded to the scene, where the structure's roof eventually collapsed.
"When we arrived it was well-involved," said Carl Baker, spokesman for the Redlands Fire Department. "The fire got going really quickly. Heavy flames, heavy smoke."
Employee Richard Rey drove to the location, where his shift had ended hours earlier.
"I left at 11 and everything was fine," he said. "As a matter of fact, the day before, we get a meeting every time. And they're like, 'OK, because of earthquakes, make sure the exits are safe and we have access to fire extinguishers.' And look what happens now."
As firefighters gained control of the fire, authorities allowed morning rush hour traffic to flow again on the 10 Freeway.
No injuries were reported.
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The cause of the fire remains under investigation.
The Associated Press contributed to this report