Mrs. Obama and family members traveling with her helped paint a mural at a clinic that treats HIV/AIDS infected children. The disease is a major public health challenge in Botswana, a country of 2 million people, including about 300,000 HIV/AIDS carriers.
The first lady then spoke at a women's leadership luncheon, where she called Botswana "a thriving democracy" with a fast-growing economy that embodies "a vision of Africa on the move."
She also planned a brief visit with President Ian Khama before taking the family to dinner at a nature park.
Mrs. Obama flew to Botswana from Cape Town. She, her daughters Malia, 12, and Sasha, 10, were welcomed with a performance of traditional African dances performed by a group of children ages 6 to 18.
At Cape Town Stadium in South Africa Thursday, the first lady and former Anglican Archbishop Desmond Tutu did some push-ups with children.
It was part of an HIV prevention effort to encourage children to make safe and healthy choices. She then had dinner with Oprah Winfrey, who's in South Africa to accept an honorary degree.
The first lady's mission began last Monday in South Africa. She returns Monday to the White House.
The Associated Press contributed to this story