Ex-NASA chief Sean O'Keefe was also believed to be aboard, but it was unclear whether he was among the dead.
Stevens' family has been notified that the 86-year-old was among those killed in the crash Monday night, family spokesman Mitch Rose told The Associated Press.
Rescuers arrived on helicopter early Tuesday and were giving medical care to survivors, Alaska National Guard spokesman Maj. Guy Hayes said. He offered no additional details, except that there were potential fatalities.
Alaska officials reported that nine people were aboard the aircraft and that "it appears that there are five fatalities," NTSB spokesman Ted Lopatkiewicz told The Associated Press in Washington.
Lopatkiewicz said the NTSB is sending a team to the crash site outside Dillingham, located in northern Bristol Bay about 325 miles southwest of Anchorage. The aircraft is a DeHavilland DHC-3T registered to Anchorage-based GCI.
Federal Aviation Administration spokesman Mike Fergus said the plane took off at 2 p.m. Monday from a GCI corporate site on Lake Nerka, heading to the Agulowak Lodge on Lake Aleknagik. He didn't know if that was the final destination or a refueling stop.
The GCI lodge is made of logs and sits on a lake, and photos show a stately main lodge room with a large imposing stone fireplace, a leather sofa and a mounted caribou head on the wall.
Fergus said the plane was flying by visual flight rules, and was not required to file a flight plan.
Stevens and O'Keefe are fishing buddies and the former senator had been planning a fishing trip near Dillingham, friend William Canfield said. The flights at Dillingham are often perilous through the mountains, even in good weather.
Hayes said the Guard was called to the area about 20 miles north of Dillingham around 7 p.m. Monday after a passing aircraft saw the downed plane. But severe weather has hampered search and rescue efforts.
The National Weather Service reported rain and fog, 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 later.
At least three crash victims were being airlifted to Anchorage, Guard spokeswoman Kalei Brooks Rupp said. She said volunteers hiked into the crash site Monday night and provided medical aid until rescuers arrived.
Lawmakers, officials in both national parties and residents in Alaska were awaiting news of Stevens' fate.
The moderate Republican was appointed to the Senate in 1968 and served longer than any other Republican in history. He was beloved as a tireless advocate for Alaska's economic interests.
The White House said Obama administration officials were closely watching news out of Alaska.
Sen. Lisa Murkowski, R-Alaska, asked Alaskans to join her in prayer for all those aboard the aircraft and their families, as did Sen. Mark Begich, D-Alaska. He called the plane crash tragic.
Begich's father, Nick Begich, who was Alaska's only congressman in 1972, was killed when his plane disappeared over the Gulf of Alaska with then-House Majority Leader Hale Boggs of Louisiana.
Stevens was one of two survivors in a 1978 plane crash at Anchorage International Airport that killed his wife, Ann, and several others. He remarried several years after the crash - he and his second wife, Catherine, have a daughter, Lily.
Over the years, Stevens directed billions of dollars to Alaska.
But one of his projects - infamously known as the "Bridge to Nowhere" - became a symbol of pork-barrel spending in Congress and a target of taxpayer groups who challenged a $450 million appropriation for bridge construction in Ketchikan.
Stevens' standing in Alaska was toppled by corruption allegations and a federal trial in 2008. He was convicted of all seven counts - and narrowly lost his Senate seat to Begich in the election the following week.
But five months after the election, Attorney General Eric Holder sought to dismiss the indictment against Stevens and not proceed with a new trial because of prosecutorial misconduct by federal prosecutors.
O'Keefe, 54, was NASA administrator for three tumultuous years. He was deputy director of the Office of Management and Budget when President George W. Bush asked him in late 2001 to head NASA and help bring soaring space station costs under control.
But budget-cutting became secondary when the shuttle Columbia broke apart during re-entry in 2003.
O'Keefe's most controversial action at NASA was when he decided to cancel one last repair mission by astronauts to the Hubble Space Telescope. He said the mission was too risky. His successor overturned the decision. The Hubble mission was carried out last year.
O'Keefe left NASA in 2005 to become chancellor of Louisiana State University. He is now the CEO of defense contractor EADS North America and oversees the bid for the hotly contested Air Force refueling jet contract.
The company said O'Keefe was a passenger on the plane. The company said it had no further information about O'Keefe's status.
The contract competition, which pits EADS against rival plane maker Boeing Co., is for a piece of what could eventually be $100 billion worth of work replacing the military's fleet of aging tankers.
Associated Press writers Mark Thiessen in Anchorage, Alaska, and Pauline Jelinek, Matt Apuzzo and Natasha Metzler in Washington, D.C., contributed to this report.