"You can't resolve it with the distribution of condoms," the pope told reporters aboard the Alitalia plane headed to Yaounde. "On the contrary, it increases the problem."
It was his first explicit statement on an issue that has divided even clergy working with AIDS patients.
Benedict arrived in Yaounde, Cameroon's capital, Tuesday afternoon to a crowd of flag-waving faithful and snapping cameras. The visit is his first pilgrimage as pontiff to the African continent.
Benedict had never directly addressed condom use, though his position is not new. His predecessor, Pope John Paul II, often said that sexual abstinence — not condoms — was the best way to prevent the spread of the disease.
Benedict said that the Roman Catholic Church is in the forefront of the battle against AIDS.
The pope said that a responsible and moral attitude toward sex would help fight the disease.
About 22 million people in sub-Saharan Africa are infected with HIV, according to UNAIDS. In 2007, three-quarters of all AIDS deaths worldwide were there, as well as two-thirds of all people living with HIV.
Rebecca Hodes with the Treatment Action Campaign in South Africa said if the pope is serious about preventing new HIV infections, he will focus on promoting wide access to condoms and spreading information on how best to use them.
"Instead, his opposition to condoms conveys that religious dogma is more important to him than the lives of Africans," said Hodes, director of policy, communication and research for the action campaign.
While she said the pope is correct that condoms are not the sole solution to Africa's AIDS epidemic, she said they are one of the very few HIV prevention mechanisms proven to work.
Even some priests and nuns working with those living with HIV/AIDS question the church's opposition to condoms amid the pandemic ravaging Africa.
The Roman Catholic Church rejects the use of condoms as part of its overall teaching against artificial contraception.
Senior Vatican officials have advocated fidelity in marriage and abstinence from premarital sex as key weapons in the fight against AIDS.
The late Cardinal Alfonso Lopez Trujillo made headlines in 2003 for saying that condoms may help spread AIDS through a false sense of security, claiming they weren't effective in blocking transmission of the virus. The cardinal, who died last year, headed the Vatican's Pontifical Council for the Family.
Benedict's African trip this week will also take him to Angola.
Africa is the fastest-growing region for the Roman Catholic Church, though it competes with Islam and evangelical churches.