The area has been selected by the government to host the £5m Great Exhibition of the North in 2018.
It was chosen above three other shortlisted bidders - Sheffield, Bradford and Blackpool.
Former Chancellor George Osborne came up with the idea as part of his Northern Powerhouse package.
Culture Secretary Karen Bradley said she was won over by Newcastle and Gateshead's "ambition", including the organisers' estimate that the exhibition will attract three million people.
By Will Gompertz, arts editor
The only potential problem I can see at this stage with the Great Exhibition of the North is the title. It sets expectations high, don't you think? What with its echoes of The Great Exhibition (1851), which was a World Fair and therefore rather different.
There was also the famous Art Treasures of Great Britain exhibition, which was held in Manchester in 1857. That was a blockbuster show if ever there was one, with around 1.3 million visitors going to take a look at the 16,000 artworks on display. It ran for just over five months.
The team behind the Newcastle-Gateshead bid are hoping to attract three million people in two months to their multi-site showcase of the North of England's contemporary arts and enterprise scene.
That's an ambitious target. I hope it, together with the hyperbolic title, doesn't overwhelm the event's programmers and lead them down the Millennium Dome-type route of worthy but dull quasi-educational installations.
It should and could be a terrific show, leaving visitors to conclude for themselves that it was a great (with a lowercase G) exhibition.
"That level of ambition really did stand out," she told BBC News. "But that doesn't mean this is just for Newcastle-Gateshead."
The 77-day exhibition will have the overarching theme of The Blazing World - The Fires of Invention.
Newcastle and Gateshead's joint bid said: "Inspired by the trailblazers of the north, the exhibition will have several cross-cutting themes for all to respond to, showing how the north's fires of invention continue to transform our world.
"Crucially, we will connect artists with scientists and inventors to work closely together, to create new artworks and respond to the great innovations of our time. Arts will meet industry in powerful and memorable ways."
The region has already proved it can host major art events, with a record 140,000 people visiting the Turner Prize exhibition when it was staged at the Baltic in 2011.
But cultural venues in both Newcastle and Gateshead have struggled in the face of local council funding cuts in recent years.
As well as the £5m for the exhibition, the government has pledged £15m for a legacy fund, which will be open to cultural organisations across the north.
Mrs Bradley said: "This is an exhibition for the whole north, and certainly through the legacy work, we are looking for bids across the whole of the north of England so we can really show everything the north has to offer."
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Newcastle and Gateshead have been selected to host a major exhibition showcasing art, design and innovation from the north of England.