More than $20 million will be divided equally between the Hunter Medical Research Institute and the Newcastle Art Gallery Foundation, thanks to the generosity of the late Valerie Ryan.

Mrs Ryan was a long-time supporter of both organisations prior to her death in November. She was 94.

Her niece, Megan McManus, said Mrs Ryan had loved her family, her friends and her travels.

She had been passionate about art and culture, knowledge and Newcastle.

"She chose the Art Gallery and HMRI to donate this wonderful gift because she believed they would do great things for the city she loved," Ms McManus said.

Other local and national charities would also benefit from additional bequests left in Mrs Ryan's will.

Mrs Ryan and her late husband, John, had invested wisely, lived modestly, and given generously to their community, Ms McManus said.

Mr Ryan, who died in 2009, was a metallurgist who established a coat hanger factory in Newcastle.

Mrs Ryan had owned a ballet store and taught shorthand and typing at TAFE.

"They were a devoted couple who valued hard work, sharing good times with friends and were great fun to be around," Ms McManus said.

"The outcome of these bequests will be a wonderful legacy to this amazing couple."

HMRI director, Professor Tom Walley, said the "true value" of the Valerie and John Ryan Bequest was "immeasurable".

"This extraordinary legacy will have a huge impact for HMRI and the health of the community we serve," Professor Walley said.

"This gift is truly transformative and will make a significant difference to research here at HMRI for many years to come. HMRI is built on generous donations from our community, and every dollar makes a difference to improving health outcomes."

Newcastle Art Gallery Foundation chair Suzie Galwey said the couple's bequest would have an enduring impact on the cultural life of the city they loved.

"Valerie was a generous donor to the Newcastle Art Gallery Foundation during her lifetime, achieving the highest level of Foundation Governor in 2014," she said. "She loved attending gallery events, and contributed to a range of projects including the commissioning of the Stuart and Sons piano and the purchase of important works by the artists Joseph Lycett, William Dobell and Brett Whiteley."

Director of Newcastle Art Gallery, Lauretta Morton, said they had been "humbled" by the generosity of the bequest.

"We are thrilled that through this extraordinary gift to Newcastle Art Gallery Foundation the legacy of Valerie and John Ryan will continue to benefit their beloved gallery and community for future generations," she said.