A friend of Stevens and O'Keefe said the two were fishing buddies and had been planning a fishing trip near Dillingham for a while. Dillingham flights are known to be dangerous through the mountains, even in good weather.
A team with the National Transportation Safety Board has been dispatched from Washington, D.C. to investigate the crash. Rescuers arrived on helicopter early Tuesday and were giving medical care to survivors.
National Guard officials said that at least three crash victims were airlifted to Anchorage. Good Samaritans hiked into the crash site on Monday night and provided medical aid until rescuers arrived Tuesday.
Authorities said the National Guard was called to the crash site at around 7 p.m. on Monday when a passing aircraft saw the downed plane outside Dillingham, located in northern Bristol Bay about 325 miles southwest of Anchorage. The aircraft is a DeHavilland DHC-3T registered to Anchorage-based cable and telecommunications company, GCI.
The Federal Aviation Administration said the plane took off at 2 p.m. on Monday from a GCI corporate site on Lake Nerka. It was heading to the Agulowak Lodge on Lake Aleknagik, but officials don't know if that was the final destination or a refueling stop.
Crews had difficulty reaching the crash site early Tuesday morning due to severe weather.
The National Weather Service reported rain and fog at Dillingham, with low clouds and limited visibility early Tuesday.
Conditions ranged from visibility of about 10 miles reported at Dillingham shortly before 7 p.m. Monday to 3 miles, with rain and fog, reported about an hour later, according to the agency.
Stevens, 86, a moderate Republican, was appointed to the Senate in 1968 and served longer than any other Republican in history.
Stevens directed billions of dollars to Alaska over the years, but one of his projects, infamously known as the "Bridge to Nowhere," became a symbol of pork-barrel spending in Congress.
Taxpayer groups targeted the project, challenging a $450 appropriation for bridge construction in Ketchikan.
President Barak Obama released a statement describing Stevens as a decorated World War II veteran who was devoted to his career and serving the people of Alaska.
"Michelle and I extend our condolences to the entire Stevens family and to the families of those who perished alongside Sen. Stevens in this terrible accident," the president said in his statement.
O'Keefe, 54, was NASA administrator for three years. Former President George W. Bush asked him in late 2001 to head NASA to help budget space station costs.
After leaving NASA in 2005, O'Keefe became chancellor of Louisiana State University. He is now the CEO defense contractor EADS North America.
AP contributed to this report.