Scottish lawmakers last year voted to call a referendum for independence from the United Kingdom, Such a vote would be conducted in 2014.
Cameron, in a statement, said economic strength, national security and international influence were at risk of diminishing in a fractured United Kingdom.
"This big question is for Scotland to decide," he said. "But the answer matters to all of our United Kingdom. Scotland is better off in Britain. We're all better off together and poorer apart."
Cameron frustrated European leaders last month when he said his constituents would "have their say" on membership in the European Union in a referendum after national British elections in 2015.
European Parliament President Martin Schulz said the announcement was part of a "dangerous game" Cameron was playing for political reasons.
The Scottish government, meanwhile, proposed an independence day for March 2016.
"An independent Scotland is not an end in itself, rather it offers us an opportunity to build the kind of country we all want to see," Scottish Deputy First Minister Nicola Sturgeon said in a statement last week.