The duo have released a hilarious video urging viewers to look after themselves and “anybody who might be suffering in silence.”
The video centres on a comic misunderstanding, before going on to reveal the serious message behind the collaboration.
In the clip, shared to the @SussexRoyal Instagram account, Sheeran, 28, jokes to the Duke of Sussex, 35, that nobody understands what it's like for “people like us.”
But while he’s referring to the fact they both have ginger hair, Harry is talking about something entirely different.
The video starts with Sheeran telling of his excitement at working with Harry.
The duke then greets him at the door to an unspecified house (suspected to be Princess Eugenie’s home, due to a photo of the royal on her wedding day being visible in the hallway), telling the pop star: “It’s like looking in a mirror.”
The pair go on to discuss what Harry describes as a “subject that's just not talked about enough.”
Sheeran says he agrees, before it becomes apparent they are talking about very different things.
Having said he has been trying to write a song about the subject, Sheeran goes on to tell the duke that “people just don’t understand what it’s like for people like us.”
Confused, Prince Harry asks what he means: “With the jokes and the snide comments,” the singer explains. “I just think it’s time we stood up and said we’re not going to take this anymore - we’re ginger and we’re going to fight.”
The duke shifts uncomfortably before telling the singer there has been some crossed wires: “Umm OK. Slightly awkward. Maybe there’s been a slight miscommunication but this is actually about World Mental Health Day.”
Sheeran responds: “Oh yeah, of course. I definitely knew that,” before deleting a title on his laptop reading: “Gingers unite.”
The pair then talk to the camera revealing the real reason for them coming together.
“Guys, this World Mental Health Day, reach out, make sure that your friends, strangers look out for anybody who might be suffering in silence,” Harry says.
“We're all in this together.”
Alongside the video clip the Instagram caption read: "It’s World Mental Health Day! Both Prince Harry and Ed Sheeran want to ensure that not just today but every day, you look after yourself, your friends and those around you.
“There’s no need to suffer in silence - share how you’re feeling, ask how someone is doing and listen for the answer. Be willing to ask for help when you need it and know that we are all in this together.”
The sharing of the video comes hours after the pair offered a teaser on the collaboration, posting a short section of the clip with the text: “Tomorrow. 10th October.”
World Mental Health Day is held annually to raise awareness about mental illness and the stigmas surrounding it.
This year the main focus is suicide prevention, with the World Federation for Mental Health choosing a new theme each year.
In the UK, someone takes their own life every two hours, according to research, and men are three times more likely to take their own lives than women - with men alone accounting for three quarters of suicides.
In 2018, there were 6,507 suicides registered in the UK, with 4,903 of them being among men.
This isn’t the first time Prince Harry has worked on a mental health campaign. He first discussed managing his mental health difficulties in a candid interview in 2017 with The Telegraph’s Bryony Gordon.
Earlier this week, he took part in a mental health film for the Every Mind Matters campaign, alongside wife Meghan Markle and the Duke and Duchess of Cambridge.
The two royal couples also spearhead the Heads Together mental health initiative.