"It would be a mistake for the US or Great Britain... to send in ground troops and overthrow the (Syrian President Bashar al-) Assad regime," he told the BBC on Saturday night.
He also said he did not think the Islamic State (IS) militant group would be defeated in his last nine months of office.
Obama, who was in London on a three-day visit, said Syria was a "heart-breaking situation of enormous complexity".
Obama said the US-led coalition would continue "to strike IS targets in places like Raqqa and to try to isolate those portions of the country and lock down those portions of the country that are sending foreign fighters into Europe".
But he said the international community would have to continue to apply pressure to all parties, including Russia, Iran and moderate opposition groups, "to sit down at the table and try to broker a transition".
Obama criticized those countries whose parliaments had not approved of action in Syria but still "want the US to do something about it". He said: "You can't have it both ways."
Talks in Geneva between the Syrian government and opposition delegations will continue into next week.