The day was established by the UN General Assembly in 2009 to commemorate the life and legacy of Mr Mandela.
Then, at 91, the South African leader asked people to celebrate him by supporting their communities.
The session will begin at 3 p.m. BST (10 a.m. EST) and will also include remarks by Deputy Secretary-General Amina J. Mohammed and General Assembly President Abdulla Shahid.
During the two-hour event, the 2020 UN Nelson Mandela Prize will be awarded to Ms. Marianna V. Vardinogianni from Greece and Dr. Morisanda Kouyate from Guinea.
This award is given every five years and recognizes people who have dedicated their lives to the service of humanity.
The special event to be held at UN headquarters in New York will focus on taking action and inspiring change.
In his speech, Prince Harry is expected to talk about the significant legacy of the South African leader, who spent 27 years in prison for his fight against segregation policies against non-white citizens in his country.
South Africa’s UN mission said his remarks “will be around the memories and legacy of Mandela and the lessons learned from his struggle and life that can help us face the new challenges in the world today.”
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A diplomat at the mission said the world still faces the same challenges the South African leader faced during his lifetime, including racism and racial intolerance, the gap between rich and poor, hunger and food insecurity.
Meghan and Harry visited South Africa with their son Archie Harrison in late September and early October 2019, which later became their final tour as members of the royal family.
On the final leg of their trip, the couple met Mr Mandela’s wife Graça Machel during a reception at the British High Commissioner’s residence.
The trio drank tea and discussed the Sussexes’ experience on the African continent during their 10-day tour.
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Ms Machal said: “It’s great to meet you. I’m sure we’ll be working together in the future. I can feel the vibe.”
Prince Harry’s mother, the late Princess Diana, met Mandela in March 1997, five months before he was involved in a car crash in Paris that claimed her life.
Diana wasn’t the only member of the royal family to meet the South African leader.
The Queen is known to have had a warm friendship with Mr Mandela.
According to his former personal assistant Zelda la Grange, Her Majesty and Mr Mandela were on a first-name basis.
In her memoir Good Morning Mr Mandela, Mrs Grange recalled: “I think she was one of the very few people who called her by her first name and she seemed to have fun with it.”
Prince Harry’s address to the United Nations today follows a visit the Sussexes made to the UN headquarters last September, when they met with Ms Mohammed.
The Deputy Secretary General said they discussed “how to engage on issues we care deeply about” – including vaccine justice, climate action, women’s economic empowerment, youth engagement and mental well-being.
Meghan and Harry were photographed leaving the building ahead of their appearance at the Global Citizen concert in Central Park.
At the event, Meghan and Harry took center stage to call on wealthier countries and pharmaceutical giants to take action for vaccine equality for COVID-19.
While the Duke will deliver the speech today, the Duchess previously addressed the UN on International Women’s Day in 2015 after being appointed UN Women’s Advocate for Women’s Leadership and Political Participation.
Among the people in the audience were Hillary Clinton and UN Secretary-General Ban Ki-moon.