Speaking exclusively to the Evening Times on a visit to the city, he said the referendum was not a factor in the decision to release the cash.
We revealed on Thursday that the UK Government is set to invest £500million over twenty years in a bold scheme that could create 28,000 jobs.
The City Deal programme may also see a new airport link. A £210m Glasgow Airport rail line was controversially scrapped by the Scottish Government in 2009.
Mr Cameron said: "I'd be doing this whether there was a referendum campaign or not because Glasgow should be and has the potential to be a great growth driver for the whole of Scotland, the whole of the United Kingdom.
"I hope it emphasises to people that Scotland can have, and Glasgow can have, the best of both worlds: the chance to take more decisions here in Glasgow and more decision as part of a devolved Scotland within the United Kingdom.
"I think the problem with the campaign to separate Scotland from the United Kingdom is, you know they've had years to prepare for this but they haven't actually answered any of the absolutely key questions which now raise massive uncertainties in the minds of voters who are now thinking about how to vote."
The Tories have enjoyed little support among Glasgow voters since the hated poll tax was imposed by former Prime Minister Margaret Thatcher.
Mr Cameron's party achieved only six per cent of the vote here at the last Scottish election in 2011, returning one list MSP. There are no Conservative MPs in Glasgow and the city elected only one Conservative councillor in the local elections in 2012.
When asked about these figures, Mr Cameron said: "We've got work to do to build back the strength of the Conservatives in Scotland but I think people can see there's a long-term economic plan that's working."
Deputy First Minister Nicola Sturgeon said the Scottish Government will match fund Mr Cameron's £500m investment in the city, a move which would see 1.6% of the £30billion block grant to Scotland diverted.
The Glasgow Southside MSP also promised to guarantee the funding if Scotland votes for independence on September 18.
Chief Secretary to the Treasury Danny Alexander, in Glasgow with Mr Cameron, dismissed the claim.
He told The Evening Times: "I'm delighted to hear the Scottish Government trust our work so much that they can make their own announcement within a couple of hours of mine, but it's not clear yet exactly how they're going to fund it … I look forward to it being made clear."