"Our thoughts and our prayers are with our friends in Europe, especially the people of Germany and Spain, following a terrible airplane crash in France," Obama old reporters at a joint White House conference with the visiting Afghan President Ashraf Ghani.
Obama said he had spoken to German Chancellor Angela Merkel about the crash.
He described the tragedy as "awful" and "heart-breaking" as many children died in the crash.
"I called German Chancellor (Angela) Merkel and I hope to speak with President Rajoy of Spain later today to express condolences of the American people, and to offer whatever assistance that we can as they investigate the awful tragedy," he said.
The airplane, a Germanwings jet carrying 150 people from Barcelona to Duesseldorf, crashed in a remote section of the French Alps.