The Homeland Security Department said the collapse did not appear to be terrorism-related, but Hennepin County Sheriff Richard Stanek said the cause was still unknown.
"All indications are that it was a collapse, not an act of someone doing it," Stanek said.
The first step of the federal investigation will be to recover pieces of the bridge and reassemble them, kind of like a jigsaw puzzle, to try and determine what happened, NTSB Chairman Mark Rosenker said.
Investigators also want to review video of the collapse, and were setting up a phone number for witnesses to call with information.
"It is clearly much too early in the initial stages of this investigation to have any idea what happened," Rosenker said.
But speculation was already beginning into what may have caused the eight-lane Interstate 35W bridge to buckle and collapse during the evening rush hour Wednesday
"It's hard to be conclusive so early, but it looks like the main support, the main steel arch, may have given way or something right near it," Richard Stehly, an expert in bridge engineering and co-founder of St. Paul, Minn.-based American Engineering Testing, told CBS News Anchor Katie Couric. "Also, the things that support the main arch, the foundations on either bank, perhaps they did. But investigators will look at everything. They will look at the materials. They will look at all the pieces of debris. And they'll find out the cause, because we need to learn the reason for its failure."
Inspections as far back as 2000 on the bridge identified both corrosion in the steel and a lot of cracking, says Stehly.
Questions are also being raised about a 2005 report in the U.S. Department of Transportation's National Bridge Inventory which rated the bridge as "structurally deficient" and possibly in need of replacement.
The report said there were fatigued details on the main truss and floor truss system. Yet it concluded there was no need to prematurely replace the bridge because of fatigue cracking, avoiding the high cost associated with such a large project.
Minnesota Gov. Tim Pawlenty said Thursday that there was no indication from that and other reviews that the bridge should be shut down.
"There are 80,000 bridges in the United States with that designation," Pawlenty told Couric. "Neither the federal officials nor the state officials who did the inspection indicated the bridge needed to be replaced immediately. It was something they foresaw in approximately 2020.
"Clearly, there was fatigue, but it wasn't uncommon and not unlike many bridges," Pawlenty said. "And the inspectors who looked at the bridge, actually looked at the bridge, indicated there was no need for dramatic intervention. In other words it could be monitored and dealt with. They did not call for the closure of the bridge. Had they done that the bridge would have been closed immediately."
Pawlenty ordered an immediate inspection of all bridges in the state with similar designs.
Former NTSB chairman James Burnett was in Minneapolis when the tragedy happened. He told CBS Early Show co-anchor Hannah Storm the 2005 report "does not necessarily mean there was safety inadequacy of the bridge. There are other types of structural deficiency that may not necessarily mean there's an immediate safety problem."
The I-35W bridge, a major Minneapolis artery, was in the midst of being repaired and two lanes in each direction were closed when the bridge collapsed.
Burnett said NTSB inspectors will be looking at the inspection reports of the bridge and "examining the bridge itself and particularly the metal portions to see if reports of fatigue cracking were, in fact, accurate, and whether there was any factor that might have caused those cracks to promulgate more quickly than had been projected. They'll be looking to see if there had been any external damage to the bridge, and also whether or not the construction process may have contributed, even by vibration, to the bridge failure."
Burnett said that in the 25 years he's been following transportation safety, there have been about five interstate bridge collapses.
"Bridge collapses averaging once every five years would be not as frequent, or more frequent, than we're having plane crashes," he said.