The couple appeared deeply emotional in the strongest hint yet that they are finding public life as it stands untenable.
The Duchess's words, in which she insists she has "really tried" to adopt the British stiff upper lip before concluding it is "internally really damaging", will lend weight to fears that the Sussexes are seeking a path away from traditional royal family life.
In an explosive programme with ITV, which will attract inevitable comparison to the Panorama interview undertaken by her late mother-in-law Diana, Princess of Wales, the Duchess lays bare her profound unhappiness about life in the media spotlight.
Disclosing that her British friends had warned her away from Prince Harry when they were dating, telling her that the tabloids would "ruin her life", she said she was naive not to believe them.
Insisting she does not object to fair scrutiny, the Duchess claimed her treatment in the press had been a "different beast" and said: "I never thought this would be easy, but I thought it would be fair."
The Duke and Duchess will now take six weeks away from Royal life later this year to focus on their family, splitting it between the UK and US.
They have previously been reported to be considering spending more time out of Britain, with the Duke saying living in Africa would be "amazing" if it were not for logistics making it too difficult.
Both the Duke and Duchess have recently launched separate legal battles against the tabloid press, with the Duke issuing an extraordinary statement earlier this month outlining their distress.
In a series of dramatic disclosure on the ITV documentary, he has now spoken of his own mental health setbacks, and said: "I will not be bullied into playing the game that killed my mum."
The tabloids will destroy your life
Asked about the "pressure" she is under and the "brave face" the couple put on, the Duchess hesitated on camera before admitting the situation was "hard".
"I don't think anybody could understand that," she said. "In all fairness, I had no idea.
"Which probably sounds difficult to understand here.
"When I first met my now-husband, my friends were really happy because I was so happy.
"But my British friends said to me: I'm sure he's great but you shouldn't do it because the British tabloids will destroy your life.
"And I very naively - I'm American we don't have that there - thought what are you talking about? That doesn't make sense, I didn't get it. So yeah, it's been complicated."
Appearing to hold back tears, she said: "Not many people have asked if I'm okay. But it's a very real thing to be going through behind the scenes."
Surviving, not thriving
On whether she could cope with life in the spotlight as it stands, and "put up with this", the Duchess explained she hoped for more out of life as a newlywed and new mother.
"I've said for a long time to H - that's what I call him - it's not enough to just survive something, right?" she told Bradby.
"That's not the point of life. You've got to thrive, you've got to feel happy.
"I've really tried to adopt this British sensibility of a stiff upper lip. I've tried, I've really tried.
"But I think that what that does internally is probably really damaging.
"The biggest thing that I know is that I never thought this would be easy. But I thought it would be fair. And that's the part that's really hard to reconcile."
Of the future, she said: "I don't know. You do just take each day as it comes."
A different beast
Pressed on the privileges of Royal life, in which public money and platform require some degree of media scrutiny, she conceded she could accept it "when things are fair".
"If I do something wrong, I'm the first one to say 'oh my gosh, I'm so sorry, I would never do that'," she said.
"When people are saying things that are just untrue - they've been told they're untrue but they're still allowed to say them...I don't know anyone in the world that would feel like that's okay.
"And that's different than just scrutiny. That's...what would you call that? It's a different beast, its a really different beast.
"I think the grass is always greener. You have no idea. It's really hard to understand what it's like.
"I know what it seems like it should be ... It's a very different thing."
The Duchess did not expand on which tabloid stories, which include reports on the couple's private jet use and public spending on Frogmore Cottage, she was referring to.
Both Duke and Duchess are now suing newspapers through existing legal channels, and have sought redress on some stories through press regulator IPSO.
"The rest of our lives"
The interview will raise inevitable questions about the future of the Sussexes' lives in Britain, with previous reports suggesting they had once been considering an extended stay in Africa or more time in the Duchess's home of America.
The Duke told Bradby it would be "amazing" to live in Cape Town, but conceded the logistical difficulties would prove too much .
"I don't know where we could live in Africa at the moment," he said in an interview during the tour.
"We have just come from Cape Town. That would be an amazing place to be able to base ourselves, of course it would, but with all the problems that are going on there, I just don't see how we would be able to really make as much difference as we want to without the issues and the judgment of how we would be with those surroundings.
"I think it is a very hard place to live when you know what is going on and then you are again slightly disconnected from it.
" He separately told members of the public in South Africa that his baby son Archie Mountbatten-Windsor was "happiest" on the continent, finding his voice on his first visit to show his excitement.
'This is just part of our love story
The Duchess described the trip as "a lot with a five-month old".
Asked whether it was tiring, she said: "Well life is, but any mum can relate to that. But he's doing really well, he's sleeping really well."
On Archie's meeting with Archbishop Desmond Tutu during the tour, the only time he was photographed on an official engagement, she said: "It's not lost on us what a huge and significant moment that is.
"Archie will look back at that in so many years and realise he was so fortunate to have this moment with one of the best and most impactful leaders of our time. It's really special."
Speaking of the significance of her family coming to the very area scarred by apartheid, and her choice to describe herself as a "woman of colour" during her first speech of the trip, the Duchess said she hoped her marriage to the Duke would not be seen through the prism of race.
"I would hope that the world will get to the point where you just see us as a couple who are in love," she said.
"I don't wake up everyday and see us as anything other than being who I've always been. I'm Meghan and I married this incredible man. This to me is just part of our love story."
Of her speech, in which she told women in a township she was there as "their sister", she said: "For me, when I chose to add those words into the speech, it was really the last minute.
"I said to Harry, 'what do you think if I add this in?' I don't know, it just feels right.
"And he very kindly and supportively said if that's what feels right then that's what you should say.
"Because it's true: like, before I was part of this [Royal] family that's how I identified. With people and connection.
"As a mother now, as a wife now, but just as a woman - as a woman of colour - which has been brought to the forefront in a more prominent way."
The Most Important Thing
After agreeing that she is "struggling" with her current situation, the Duchess attempted to end her interview "Harry & Meghan: An African Journey" on an upbeat note.
"That's okay," she said. "The good thing is I've got my baby and I've got my husband and they're the best."
But as Bradby concluded: "If taking it one day at a time does not prove enough? If this is existing not living? What then?"
