"This election, I'm not going to be able to vote in the US, and many of you may not know that I haven't been able to vote in the UK my entire life," he said in the footage captured in the lush garden of their new $32 million home in California.
The broadcast is part of the unveiling of Time magazine's 2020 list of the world's 100 most influential people. Harry and Meghan did not make the cut this year, after scoring a spot in 2018.
It was broadcast on the US's ABC network today, coinciding with "national voter registration day".
During the address, the Duke urged Americans to "reject hate speech" as the election approaches.
"As we approach this November, it's vital we reject hate speech, misinformation and online negativity," Harry said.
Meghan, who will be the first ever British royal family member to publicly vote in an election, went on to encourage Americans to register.
"Every four years we are told the same thing, that this is the most important election of our lifetime. But this one is," the Duchess, wearing black trousers and a brown shirt, said to the camera.
"When we vote our values are put into action and our voices are heard. Your voice is a reminder that you matter, because you do and you deserve to be heard."
They both urged Americans to be wary of their treatment of others online.
"What we're exposed to online seeps into how we engage with each other offline. It can train us to be kind, or it can train us to be cruel," Meghan said.
Harry added: "But when the bad outweighs the good, for many, whether we realise it or not, it erodes our ability to have compassion and our ability to put ourselves into someone else's shoes.
"Because when one person buys into negativity online, the effects are felt exponentially. It's time to not only reflect, but act."
At the beginning of the video, the couple recognised those named on the Time list, and the work they have done.
"Tonight reminds us of how important it is to watch out for each other, to care for each other and to inspire each other," Harry said.
"We are incredibly proud to join you in this historic moment in time."
Over on Twitter, fans were full of praise for the couple's speech.
"Really never thought I'd see this day come!" a follower gushed.
"Remarkable indeed Clapping hands sign & am glad to be a part of it. #PowerCouple whether they recognize (sic) it or not, we look up to them and are not worthy to be sharing this time with such P. O. W. E. R!! #BlessUp."
Another weighed in: "Bravo to Meghan & Harry for using their platform to remind everyone of the vital importance of voting to create positive and progressive change in society. I'm so glad that Meghan is back in her element in her home country."
"A simple yet important message to exercise kindness and compassion. A call to action to vote and make our voices be heard. Well done, Harry and Meghan. It's so good to see them!," one said.
Meanwhile, some followers were momentarily distracted by the couple's dog Pula wandering into the shot.
"Who saw Pula rambling in the background?" one pointed out.
Others were simply distracted by the expansive green surrounds.
"Look at the beautiful yard Archie, Pula and Guy have to play in," one fawned.
