Prince Harry and Meghan joined New York City mayor Bill de Blasio and Governor of New York State Kathy Hochul at the skyscraper's observatory.
One World Trade Centre was built on the site of the original twin towers and the visit comes just two weeks after the 20th anniversary of the September 11 attacks.
WATCH: Prince Harry and Meghan Markle visit One World Observatory
To mark the anniversary earlier this month, Harry and Meghan paid tribute by changing the homepage of the Archewell website to display the names of the almost 3,000 people who lost their lives.
The couple both donned black ensembles for their visit as a mark of respect, with Meghan wearing a high-neck sweater with trousers underneath a long coat.
The Duke and Duchess were asked if they were enjoying their visit to New York, with Meghan replying: "It's wonderful to be back."
Afterwards, Harry and Meghan paid their respects with a visit to the 9/11 memorial on the ground floor.
The couple were greeted by a crowd as they departed, with Meghan giving fans a thumbs up as one congratulated them on the birth of Lilibet.
Harry and Meghan joined New York City mayor Bill de Blasio
The couple will also attend the 24-hour broadcast Global Citizen Live being staged in New York's famous Central Park and around the world.
It is part of a number of shows being held in cities as varied as London to Lagos by the organisation Global Citizen, with artists like Ed Sheeran, Sir Elton John, Kylie Minogue, Metallica and Coldplay scheduled to perform.
The Duke and Duchess of Sussex have advocated for vaccine equity and urged people to support the Global Citizen COVAX campaign in honour of their son Archie's second birthday in May.
Meghan waved to the waiting crowds
Harry also made a solo appearance at Global Citizen's VAX Live concert back in May. The royal spoke for three minutes about the importance of making vaccinations borderless and called for them to be "distributed to everyone everywhere" at the star-studded charity concert.
Ahead of their first appearance in New York, Harry's sustainable tourism initiative, Travalyst announced that Google will be joining its coalition as a partner alongside existing partners, including Booking.com, Skyscanner, Trip.com Group, Tripadvisor, and Visa.
The Sussexes met with Governor Kathy Hochul and NYC Mayor Bill De Blasio
Meghan last visited New York publicly in September 2019 when she attended the US Open tennis tournament to cheer on BFF, Serena Williams.
Her closest friends, including Serena and Amal Clooney, also organised a baby shower for the Duchess at New York's luxurious Mark Hotel in February 2019 ahead of the birth of Harry and Meghan's first child, Archie.
The Sussexes now reside in Montecito, Santa Barbara, after stepping back from royal duties in March 2020.
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