In the early hours of Friday morning, 63 people set out on a darkened road from McDonald Jones Stadium bound for Manly.
They are walking across the weekend for The Big Three trek, a bi-annual event raising money to fight brain cancer.
The group will arrive at Four Pines Park in Sydney's northern beaches after a 150km journey and thousands of dollars raised.
Joining with the Mark Hughes Foundation, the trek is set to reach $250,000 in general donations, with more given to the efforts of individual walkers.
Founder Luke Alexander told NRL the support was "incredible" as the event, now in its third consecutive year, grew "year after year".
"A lot of the people [walking] have been touched by brain cancer in some way so to see everyone come together and get behind the cause is what it's all about," Mr Alexander said.
Wife of Mark Hughes and foundation co-founder, Kirralee Hughes, told the Newcastle Herald support out of Newcastle has been "simply amazing."
"A lot of people are hurting at the moment with the cost of living and we are just so grateful for everyone who supports us," she said.
Place manager of Newcastle's The Station, Sally Leacy, is just one of the people taking on the trek.
Her fundraising goal of $5,000 has already been far-surpassed. On Friday afternoon, her page sat just shy of $8,000.
The walk signposts NRL's Beanie for Brain Cancer 2023 round, which kicked off on Thursday night.
Spearheaded by the Mark Hughes Foundation, Beanies for Brain Cancer hopes to raise $3.5 million during the round.
NRL CEO Andrew Abdo said the initiative is an "extraordinary measure" of backing rugby league fans.
"Mark's dedication continues to highlight what an extraordinary person he is, and the public's support of his story and his foundation are also great examples of the rugby league community coming together for an important cause," Mr Abdo said.
Since 2017, seven rounds of the initiative have raised over $19 million dollars. The one millionth beanie is expected to be sold in the 2023 round.
"That's one million opportunities for life-changing research which Rugby League through the Mark Hughes Foundation has provided," Mr Abdo said.
Founder Mark Hughes said sales of beanies contributed to "better research" but more funds were needed to complete the work.
"[This has] brought together the best experts in the field to collaborate for a cure and change the lives of thousands of patients diagnosed with brain cancer each year," He said.
"This drives critical research, education and health care improvements at a national scale."
Games will be played in Sydney, Auckland, Melbourne, Canberra, Townsville and Brisbane.
Beanies can be bought at Lowes Australia stores or online at www.markhughesfoundation.com.au.
