The Airbus A320 plane was operated by Lufthansa's Germanwings budget airline, and lost contact with air traffic control about an hour after it took off, the airline said.
A French military helicopter located the wreckage of the plane near the town of Barcelonnette in the French Alps, about 65 miles north of Nice, Reuters reported.
French Prime Minister Manuel Valls told parliament on Tuesday that a helicopter at the crash site confirmed that there were no survivors.
The plane was carrying at least 144 passengers, two pilots and four flight attendants, according to Germanwings.
Airline officials said 67 German nationals are thought to have been on board. They said the passenger manifest included two babies.
Earlier, Spain's deputy prime minister said 45 of the passengers appear to be Spanish. French President Hollande said it was unlikely that French citizens were on board.
An spokesman for the French interior ministry told BFM television that the crash site is at 2,000 meters (6,500 feet) altitude and extremely remote, indicating "an extremely long and extremely difficult" search and rescue operation may be ahead.
Mayor of Barcelonnette Pierre Martin-Charpenel told HuffPost all emergency staff has been mobilized for the search, centering on the area of Méolans-Reve, 15 kilometers (9 miles) outside of Barcelonnette.
A local weather official said the search might be impeded by weather conditions. "There will be a lot of cloud cover this afternoon, with local storms, snow above 1,800 meters (5,900 feet) and relatively low clouds. That will not help the helicopters in their work," the official told Reuters.
A local official who visited the crash site on Tuesday said that the airplane was completely destroyed. "There's nothing left but debris and corpses," Christophe Castaner tweeted.
Aircraft manufacturer Airbus and the airline said they were working to confirm the details of the crash. "We do not yet know what has happened to flight 4U 9525," Lufthansa said in a statement. "If our fears are confirmed, this is a dark day for Lufthansa. We hope to find survivors."
The cause of the crash was not immediately clear. French police told the Associated Press that there did not appear to be turbulence or low cloud ceiling in the area. Germanwings said the plane started losing altitude one minute after it reached cruising height, and continued to descend for eight minutes before the crash.
The aircraft was built in 1991 and operated by Lufthansa and Germanwings, which was founded in 2002. The A320 is Airbus’s best-selling jet family, with more than 6,000 planes in operation. Airbus said last year that 3,606 A320 jetliners were in use around the world. In December, another A320, Indonesia AirAsia 8501, crashed into the Java Sea, killing all 162 passengers and crew.