Harry, who now lives near Los Angeles with his wife Meghan and their son, Archie, called for vaccines to be "distributed to everyone everywhere" during his speech at the concert titled, "Vax Live: The Concert to Reunite the World."
The 36-year-old prince also used his speech to thank front-line workers, many of whom were in the audience at SoFi Stadium in Los Angeles for the concert taping Sunday.
"We are at a defining moment in the global fight against COVID-19. Tonight is a celebration of each of you here, the vaccinated front-line workers in the audience and the millions of front-line heroes around the world," Harry said. "You spent the last year battling courageously and selflessly to protect us all. You served and sacrificed, put yourselves in harm's way and with bravery knowing the costs. We owe you an incredible depth of gratitude, thank you."
Meghan, who is pregnant with the couple's second child, and Harry were announced last week as campaign chairs of "Vax Live: The Concert to Reunite the World," an international COVID-19 vaccination effort organized by Global Citizen.
The concert -- which will also feature President Joe Biden, first lady Jill Biden and Vice President Kamala Harris along with celebrities including Selena Gomez, Jennifer Lopez and Ben Affleck -- will be broadcast on Saturday, May 8.
"None of us should be comfortable thinking that we could be fine when so many others are suffering. In reality, and especially with this pandemic, when any suffer, we all suffer," Harry also said in his remarks. "We must look beyond ourselves with empathy and compassion for those we know, and those we don't. We need to lift up all of humanity and make sure that no person or community is left behind. What we do in this moment will stand in history and tonight. We stand in solidarity with the millions of families across India who are battling a devastating second wave."
Harry's appearance at the concert marked his first public appearance since the funeral of his grandfather, Prince Philip, last month.
The funeral was the first time Harry had seen his family in over one year, when he and Meghan stepped down from their roles as senior, working members of the royal family. Meghan did not travel with Harry to the U.K. for the funeral due to her doctor's advice.
Harry and Meghan's decision last year to step down as senior working royals caused divisions within the royal family, a family that Prince Philip had been widely credited as holding together throughout his 73-year marriage to Queen Elizabeth.
The family tensions spilled into public view after Harry and Meghan's tell-all interview with Oprah Winfrey in March, during which Harry told Winfrey a "lack of support" and "lack of understanding" led to his and Meghan's rocky departure from their royal roles.