Meghan, Duchess of Sussex who will give a key address on equality, was dressed in a vivid red, high-necked sleek trouser suit.
She smiled and held hands with the duke as they made their way through the auditorium to huge cheers.
The couple sat centre stage on a bench as they joined One Young World counsellors to watch the flag bearers enthusiastically parade the flags of more than 200 countries during the opening ceremony.
The duchess, with her hair in a ponytail and a clapper her hands, swayed in time to the music, which included Dancing in the Streets and Respect.
The former Suits star’s opening speech was her first in-person address in the UK since quitting as a senior working royal amid the "Megxit" crisis more than two years ago.
Meghan Duchess of Sussex through the years — in pictures
The Duchess of Sussex declared it was “very nice to be back in the UK” as she took centre stage in Manchester to tell young leaders: “You are the future … you are the present."
Meghan told the 2,000 delegates how her life had changed when she last joined the summit in London in 2019, singling out her role as a wife and a mother but making no mention of becoming a senior royal the year before.
“I joined you in London in 2019 and by that point, it’s fair to say, my life had changed rather significantly," she said.
"I was now married, and I was now a mum,” she said, leaving a pause at the end, which was filled with huge cheers from the audience.
“My world view had expanded exponentially, seeing the global community through the eyes of my child [Archie]."
Meghan is a counsellor for the organisation and the conference brings together about 2,000 young leaders from more than 190 countries.
The couple also met a group of delegates doing “outstanding work on gender equality”, One Young World said.
The trip comes days after Meghan’s interview with The Cut magazine, in which she said it takes “a lot of effort” to forgive and hinted that she can “say anything”.
She said that “just by existing”, she and Harry were “upsetting the dynamic of the hierarchy” before they stepped down as senior working royals in 2020.
Prince Harry and his wife Meghan arrive for jubilee thanksgiving service — video
Their next stop will be Germany for the Invictus Games Dusseldorf 2023 One Year To Go event, which is taking place on Tuesday.
They will then return to the UK for the WellChild Awards in London, where Prince Harry will deliver a speech on Thursday.