Flight 4U9525 disappeared from radar around 45 minutes after leaving Barcelona in Spain for Dusseldorf in Germany at 10am local time.
It is believed to have come down in the Digne area of southern France.
French President Francois Hollande confirmed the crash and said he expects there to be "no survivors".
Reports suggest there were 142 passengers and six crew on board.
The plane appears to have come down in a very remote area near a ski resport.
Germanwings has scheduled a press conference for 3pm today.
The Spanish President Mariano Rajoy has just tweeted about the "tragedy".
"Dismayed by the air accident in the Alps. A tragedy. We're working with the French and German authorities on the investigation," he wrote.
Looks like plane came down not far from a ski piste. Helicopters appear to be the best/only transportation into the area. #germanwings
— Andy Lines (@andylines) March 24, 2015
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