A massive $48 million renovation has more than doubled the gallery's exhibition space, creating an additional 1600 sq m for its collection, as well as temporary shows.
"I often say to people we're growing up finally, to be the modern gallery that the city deserves," said gallery director Lauretta Morton.
The project took almost four years and has expanded the institution from five gallery spaces to 13.
While visitors were allowed to return to a small section of the gallery last September, all 13 spaces are now open to the public for the first time.
The ground floor will always be free to enter and dedicated to the permanent collection, said Morton.
A weekend of celebrations is under way to mark the reopening, with a Friday night street party featuring Hunter Valley electronic/pop duo Kinder, a temporary sculpture park and even a pop-up tattoo parlour.
The launch features the major exhibition Iconic, Loved, Unexpected, presenting almost 500 works from the collection as well as a series of new commissions.
The gallery's original brutalist building was officially opened by Queen Elizabeth II in 1977 and the expansion by architects Clare Design, Smith and Tzannes Architects and Arup Engineers, has been built in a similar style.
Importantly for visitors, it also includes a cafe and gallery shop for the first time.
The collection is more than five times what it was in 1977 with more than 7000 artworks, making it one of the most significant outside Australia's capital city institutions.
The gallery regularly loans works to state galleries, as well as internationally: artworks by Emily Kame Kngwarreye are currently on show at the Tate Modern in London.
One of the new galleries is dedicated to the late artist Margaret Olley, who moved to Newcastle in the 1960s, painting the city and its harbour.
The gallery was reputedly the first public art institution to buy a painting from Australia's top-selling artist, the late Brett Whiteley, purchasing Autumn Abstract 1959.
It commissioned his well-known painting Summer at Carcoar and outside is his much-loved steel and glass sculpture Black Totem 11.
John Olsen's 1964 painting The sea sun of 5 bells has also been returned to the ceiling of the original 1977 building.
The renowned artist, who died in 2023, was born in Newcastle in 1928, just a few blocks from the gallery.
The 2026 exhibition program includes solo shows by Brian Robinson, Angela Tiatia and Anh Do, as well as works recently donated by philanthropists Simon and Catriona Mordant.
What visitors won't come to see - but is essential to the functioning of a modern gallery - is an international standard loading dock.
It's a game changer for the valuable loans from other institutions that are vital for temporary shows, said Morton.
Previously, artworks including valuable loans had to be unloaded in the open, with truck drivers having to navigate past nearby trees, she said.
The renovation has been part-funded by the federal and NSW governments, and the Newcastle Art Gallery Foundation.