Bush told reporters after talks with Botswana's President Festus Mogae in Gaborone that the first thing he wanted the leadership in Africa to know was that the US cared deeply about the pandemic in the continent.
"The people of this nation have the courage and the resolve to defeat this disease and you will have a partner in the United States of America," Bush said during a luncheon for 700 people.
"My country is acting to help all of Africa in turning the tide against AIDS. This is the deadliest enemy Africa has ever faced and you will not face this enemy alone," he added.
Bush praised Mogae for being on the "forefront of dealing with this serious problem by first and foremost admitting that there is a problem and then by working to put a strategy in place to prevent and treat it."
Mogae toasted Bush saying Washington had "answered his call" in the fight against AIDS by increasing funding for a joint testing and counselling programme.
With a population of just 1.68 million Botswana represents the best and worst of Africa.
Thanks mainly to its diamonds, it boasts among the highest average per capita incomes on the continent -- $3,100 per year.
But the mostly desert nation shares Africa's AIDS agony and is considered the world’s worst affected. One in five people has HIV/AIDS, with the virus estimated to afflict about 40 percent of its sexually active population.
Bush returned to South Africa on Thursday after his visit to Botswana, the third stop on his five-nation Africa tour. On Friday, the US president visits Uganda and Nigeria.