The aptly named track is being used by the Uluru Dialogue campaign, the architects of the Uluru Statement, to gain support for a successful referendum.
It's the first time Farnham has ever granted permission for the anthem to be used for commercial use.
The advertising film starts in the 1980s, when the song was released, and follows a family through the years as they witness several key moments in Australia's history.
These moments include: the 1967 referendum, allowing the government to make laws for the Aboriginal and Torres Strait Islander people and include them in the census; the 1992 Mabo land rights decision; Australia's America's Cup win in 1983; the Uluru handback in 1985.
It also shows Cathy Freeman's gold medal win at the Sydney 2000 Olympics, the 1996 gun reform, the 2008 apology to the Stolen Generations and the 2016 marriage equality plebiscite.
Farnham has called the track life-changing, and hopes it can do the same for others.
"I can only hope that now it might help, in some small way, to change the lives of our First Nations Peoples for the better," Farnham said .
Tim Wheatley, Farnham's close friend and son of his late manager Glenn Wheatley, said the iconic song is not aligned with politics but with humanity.
"You're the Voice is not aligned with any political party," Wheatley said.
"It's a song for all Australians. Always has been, always will be."
He added: "Both John and my father have fiercely protected this song's use for decades, I think, for this very moment."
Cobble Cobble woman and co-chair of the Uluru Dialogue, Professor Megan Davis, said You're the Voice is the nation's unofficial anthem.
"It is an empowering message," Davis said in a statement.
"History isn't just something we witness and observe, but something we ourselves can influence.
"And now we all have a voice in what happens at this critical moment, and we must use it."
She said they were proud to announce the partnership between John Farnham and the Uluru Dialogue's History Is Calling campaign.
"The number one question Aussies have asked me for six years is 'Have you thought of Johnny Farnham and You're the Voice?'," Davis said.
"We hope You're the Voice will show Australians that we all have a role to play in making this referendum a success, and that it will inspire people to walk with us on this movement for a better future."
The ad will premiere tonight ahead of the referendum, which will be held on October 14.