And he has called on the Scottish Government to match the massive cash injection aimed at strengthening the economy of the city and surrounding area.
Mr Cameron announced the financial investment ahead of a visit to Scotland at which he will provide further details of the City Deal package.
The city will be the first in Scotland to benefit from City Deal status which is an agreement between the Treasury and a city region.
It involves the transfer of significant additional economic power and finance in exchange for a disciplined and detailed plan to invest in the area's economy.
Westminster says the City Deal will lead to the creation of more than 28,000 new jobs in the Glasgow area over the next 20 years and will eventually generate around £1.75billion of economic growth in the city every year.
It will also provide targeted support to more than 4000 ill or disabled people in work or looking for work and to 15,000 young people over the next three years.
City council leader Gordon Matheson has repeatedly warned Glasgow is losing out to major English cities like Manchester, Leeds and Liverpool which have already been awarded City Deal status.
And he has insisted there is nothing in Scottish policy which comes close to the potential of the UK scheme.
David Cameron made the announcement in conjunction with Chief Secretary of the Treasury Danny Alexander.
The Prime Minister said: "Glasgow is one of the United Kingdom's greatest cities and like Liverpool, Manchester and Leeds, it not only has a proud history but it also has a fantastic future.
"The city has prospered from industry, innovation and culture but has also been held back by unemployment and skills shortages."
He said that mattered for the whole of the UK as long lasting prosperity would only happen if all the country's regions and cities were fulfilling their potential.
Mr Cameron added: "For too long, governments in London and Edinburgh have acted as though taking powers away from Britain's great cities is the best way to create growth, rather than trusting the people living there to find their own specific solutions to meet their own unique needs.
"But not any more."
The Prime Minister said the City Deal is a partnership between Glasgow and the UK Government but would also be seeking a partnership with Holyrood.
He added: "This shows how Glasgow can benefit from having the best of both worlds - a devolved Government in Scotland and the broad shoulders of the UK Government that can use its influence and resources to unlock vital investment.
"Building on this significant investment we are inviting the Scottish Government to match the UK Government contribution."
A spokeswoman for the Scottish Government said it had tried several times to "engage with the UK Government to secure the best outcome for Glasgow", and looked forward to seeing the details of the City Deal.
"This represents £25 million per annum over the next 20 years. The Scottish Government has been making substantial investment in Glasgow over the years, including over £380 million towards the Commonwealth Games," the spokeswoman said.
"We will be working to ensure this UK proposal dovetails with the work of the Scottish Cities Alliance and our existing investment in infrastructure. The Scottish Government is working individually and collectively with all Scotland's cities to optimise economic growth for the benefit of the whole of Scotland."
The cash boost will go towards a new fund which will support infrastructure projects such as a new airport rail link, major improvements to the region's road and bus network and the development of new business sites.
In 2006, the Scottish Parliament passed the Glasgow Airport Rail Link which would have resulted in trains between Central Station and the airport.
However the £210million scheme was scrapped three years later as part of spending cuts.
Glasgow, North Lanarkshire, South Lanarkshire, East Renfrewshire, Renfrewshire, Inverclyde and West Dunbartonshire councils have pledged £130m to the new infrastructure fund.
City council leader Gordon Matheson described the announcement as historic for the city and surrounding area.
He said: "This is the start of an era of transformation in the Glasgow city region.
"This truly historic city deal is the biggest in the UK and the first in Scotland.
"It will lead to more and better jobs, new companies which survive and grow and a massive expansion in modern high tech industry.
"City regions really are the engines of national economic growth and I have long argued that devolving more power to our cities is the best way to grow the Scottish and British economies.
"We have been able to secure a great deal from the UK Government and I know the Scottish Government will want to ensure this deal is a success.
"This deal also shows the strength of the partnership between the local councils in the Clyde Valley.
"We have great strengths - a stock of land which can be brought into productive use, brilliant housing and amenities to attract and retain the best people and universities which are educating the next generation of scientists and engineers.
"It is hard to overestimate how important this is for Scotland."
The statement from David Cameron, Prime Minister and Danny Alexander, Chief Secretary to the Treasury:
Glasgow is one of the United Kingdom's greatest cities and like Liverpool, Manchester and Leeds, it not only has a proud history it also has a fantastic future.
The city has prospered from industry, innovation and culture but has also been held back by unemployment and skills shortages. This matters for the whole of the UK, because sustainable prosperity will only happen if all our regions and cities are fulfilling their potential.
And for too long governments in London and Edinburgh have acted as though taking powers away from Britain's great cities is the best way to create growth, rather than trusting the people living there to find their own specific solutions to meet their own unique needs.
But not any more.
This city deal is a partnership between Glasgow and the UK Government and we will also seek a partnership with the Scottish Government - this shows how Glasgow can benefit from having the best of both worlds: a devolved Government in Scotland and the broad shoulders of the UK Government that can use its influence and resources to unlock vital investment.
Glasgow plans to create a £1.1 billion infrastructure fund that will support projects such as the city centre-airport rail link, major improvements to the region's roads and bus network, and the development of new employment sites.
The UK Government is offering £500 million of new funding to support this genuinely ambitious proposal, with local authorities in the region providing a further £130 million. Building on this significant investment we are inviting the Scottish Government to match the UK Government contribution.
This vote of confidence in Glasgow will also help generate private-sector money so businesses can flourish.
In exchange Glasgow will take active measures to further reduce unemployment and help move people in low-paid jobs into higher paid ones.
These are genuine powers that will change the fortunes of people across the region by creating new jobs, improving transport networks, boosting businesses and providing skills to young people and the long-term unemployed
So from tomorrow, those who know Glasgow best - the people who live and work here - can decide where this investment can benefit them and their families most. And local leaders will now have the final say in how this money should be spent.
We want Glasgow to have the freedom, power and tools to innovate and succeed for a brighter, more prosperous future. That's why we applaud the ambitious aim to invest in infrastructure and attract private investment to help local business leaders establish Glasgow as a world leading city.
Only weeks before the Commonwealth Games showcases Glasgow to the world, this city deal sends a very clear message that the region is open for business.
People make Glasgow - and it is the hardworking people of Glasgow that are helping build a stronger economy and fairer society, creating a lasting legacy for generations to come.