The NTSB sent a team to the site to investigate the crash, about 20km from the city of Dillingham in the sprawling state's southwest.
"Local authorities are reporting that there are survivors and a rescue operation is underway. No other details are available at this time," Guy Hicks, a spokesman for EADS North America said on Tuesday.
The Alaska National Guard said that medical personnel had reached the scene of the crash, which apparently occurred in poor weather on Monday.
Major Guy Hayes, a National Guard spokesman, said his organisation was called to an area 30km north of Dillingham, after a passing aircraft saw the downed plane.
The wilderness area where the aircraft went down is known for its scenic beauty.
Stevens was flying to the Agulowak Lodge, owned by the same company which owns the single engine plane that crashed, The Anchorage Daily News reported.
The former Alaska senator lost a tight race in November 2008, just one week after he was found guilty of corruption regarding gifts he received from an oil services firm.
O'Keefe, the 54-year-old chief executive of the EADS's North America operations, had been on a private trip, a company spokesman said.
Transport by small plane is common in Alaska, where weather, long distances and an incomplete highway system make road travel difficult.
The crash is the third in less than two weeks in the sparsely populated state.