The Duke and Duchess of Cambridge and Prince Harry want to "help change the national conversation" on mental health.
They are leading a campaign called Heads Together which will be the biggest single project they have undertaken together.
It will be a partnership with charities with experience in tackling stigma, raising awareness, and providing help for people with mental health challenges.
The campaign will be the 2017 Virgin Money London Marathon Charity of the Year, taking the baton from the NSPCC.
A spokesman for William, Kate and Harry said: "Through their work with young people, emergency response, homeless charities, and with veterans, their royal highnesses have seen time and time again that unresolved mental health problems lie at the heart of some of our greatest social challenges.
"They are passionate about tackling the stigma surrounding the issue. Too often, they have seen that people feel afraid to admit that they are struggling with their mental health. This fear of prejudice and judgment stops people from getting help and can destroy families and end lives.
"They want to help change the national conversation."
The spokesman said the three are "incredibly grateful to be working with charities who have achieved so much in the fight against the stigma that surrounds the issue".
He added: "They want the Heads Together campaign to build on the great work that is already being done across the country so that prejudice and fear no longer stand in the way of people getting the help they need.
"They want people to feel much more comfortable with their everyday mental wellbeing and have the practical tools to support their friends and family."
The team of charity partners working on Heads Together includes Best Beginnings, CALM – The Campaign Against Living Miserably, Contact (a military mental health coalition), Mind, Place2Be, The Mix and YoungMinds.