The speech is timed to celebrate the 100th birthday of the late global human rights icon.
The former US president will call on young people around the world to work towards fairer societies highlighting Mr Mandela's struggle for democracy and equal rights in South Africa.
It is one of the most high-profile addresses Mr Obama will have made since leaving office at the start of 2017. However, as has been the case with almost all of his public speeches, he is not expected to mention his successor in the White House, President Donald Trump.
“At the current moment we’re in, values that we thought were well-established — the importance of human rights, respect for diversity — in many parts of the world those values are under threat,” Ben Rhodes, a long-time Obama aide in White House, told The Associated Press. “Mandela’s life is an inspiring example of how we can overcome obstacles to promote inclusive democracy and an equitable society with tolerance of others.”
Mr Obama is expected use the annual Nelson Mandela Lecture to highlight how Mr Mandela, a Nobel Peace Prize winner, kept up his campaign against apartheid - or white minority rule - in spite of what appeared to be insurmountable odds. Mr Mandela was imprisoned for 27 years as part of his fight on charges of conspiring to overthrow the state, before emerging from Robben Island prison and going on to lead his nation.
Becoming South Africa's first black president in 1994, Mr Mandela died in 2013 leaving behind a legacy of the power of reconciliation and diversity.
Mandela, who was released from prison in 1990 and became South Africa’s first black president four years later, died in 2013, leaving a powerful legacy of reconciliation and diversity along with a resistance to inequality, economic and otherwise.
“In the US and around the world, many see recent developments that run counter to Mandela’s legacy,” Rhodes said. “This will be a globally minded speech, highlighting global trends and focusing on how, in his life, Mandela embodied perseverance," Mr Rhodes said.
Mr Obama is visiting Kenya ahead of the speech, returning to land of his father for the first time since leaving the presidency.
More about: Obama