Sir Michael Lyons, chairman of the BBC Trust, was given a glass baton in a ceremony to mark the occasion, which will now see the Corporation fitting out the studios and offices in readiness for 2,500 BBC employees working on site by 2011.
Sir Michael said: "This is the daddy of them all, the biggest relocation project the BBC has ever undertaken and redefines what the BBC is, and does, and what it means for the British people.
"This project will eventually have 15,000 more employees, a new home for the UK digital and communications industries.
"This will be the home of extraordinary creative thinking."
Building C - the biggest and first of three BBC office buildings to be handed over to the corporation today - will be home to BBC Radio 5 Live, BBC Sport and local and regional news.
MediaCity's developer Peel Media and industry support body Northwest Vision and Media are urging Merseyside firms to take advantage of the opportunities on offer at the development. They hope the site will act as a catalyst for thousands more jobs in the wider private sector, from TV production to computer games design.
The investment will represent up to £1bn to the North's economy in the coming years according to the Northwest Development Agency.
The development is part of the corporation's "Out-of-London" strategy which aims to better serve and represent audiences and spread the BBC's investment.
About 2,800 people are now directly employed in MediaCityUK's construction site, which is on Salford Quays, for many years a derelict dockland site at the side of the Manchester Ship Canal.
The site is now the largest privately-funded construction site in Europe after an initial £500m funding injection from Peel, with more than 50% of workers from Greater Manchester and 75% from the North West.
Peter Salmon, director of BBC North, said: "It is a milestone on the journey to be given the first of our new buildings, and ahead of schedule, how often do you hear that? We get things done up here."
Mr Salmon said 46% of staff in London affected by the switch north had now decided to move with the BBC.
The corporation was moving some of its biggest departments and most high profile brands, which would act as a creative catalyst for the North, he said.
"We are trying fairly hard to change the very DNA of the BBC," he added.
"Something truly remarkable and very cutting edge is taking shape on the banks of the old ship canal."
The BBC takes delivery of two more buildings, 'A' and 'B' - to house BBC Children's, BBC Learning, Religion, Radio, hundreds of technologists and the BBC Philharmonic Orchestra in the spring of 2010, creating the Corporation's second biggest base after London.

Click here to see LDP Creative's slideshow of images from MediaCity's topping-out ceremony in July.