Harry, who recently completed a four-and-a- half-month tour of duty to Afghanistan, will travel to the countries for a three-day trip on behalf of his charity Sentebale.
He will spend the first two days visiting Sentebale programmes throughout Lesotho, and on the final day, will carry out public engagements in the Maseru district of Lesotho and then attend the Sentebale gala dinner in Johannesburg.
The last time the 28-year-old third in line to the throne was in Lesotho was in June 2010 when he took his brother, the Duke of Cambridge, to see Sentebale's work as part of their first joint overseas trip.
Harry arrived back from Afghanistan less than two weeks ago. During his time there, the Prince revealed he took Taliban fighters "out of the game" from the cockpit of Apache attack helicopters and admitted he "let himself down" by romping naked in Las Vegas before his deployment.
After returning to the UK, he said he would like to dedicate more time to royal duties and charitable causes, as well as pursuing his Army flying career.
His trip will begin on February 25 with two days of private visits.
On February 27, the Prince will publicly attend the Kananelo Centre for the Deaf and the Reitumetse Church Project in Lesotho, which are two of Sentebale's community-based partners within the Letsema Collaborative Network, caring for disabled and orphaned children.
In Johannesburg, he will attend the Sentebale gala dinner, which marks the launch of the charity's fundraising drive to build a permanent centre for children and young people.
His commitment to Lesotho began nine years ago in 2004 when he spent part of his gap year in the country, working with various organisations.
The Prince was moved by the plight of youngsters he met during his time volunteering with an orphanage where many of the children had HIV and Aids.