The visit will be an opportunity for the pontiff to articulate the Vatican's position on global issues affecting the continent. Francis' predecessor, Benedict XVI, made several trips to the continent, laying out a wide-ranging vision for the African church, "Africae Munus", which included policies on women's rights, economic development and governance.
All three countries on the Pope's tour have experienced conflict over religion and identity over the past few years, albeit to varying degrees.
The Central African Republic has teetered on the brink of a genocide, as inter-community violence between Christians and Muslims flared in the security vacuum left by the country's civil war, which began in 2012. Seleka, a rebel coalition predominantly made up of Muslim fighters from the country's north, swept south and took the capital.
Since then, Seleka has handed power back to an interim civilian administration, United Nations peacekeepers have been deployed to the country and elections are scheduled for December. However, tit-for-tat attacks on civilians by former rebels and the 'anti-balaka' Christian militias have continued, and hundreds of thousands of people have been displaced within the country and across its borders.
The security situation in the country means that the papal visit remains in question. Pope Francis was due to visit a cathedral and a mosque in Bangui, the capital, and to meet with refugees.
Although its religious tensions are not on the same scale as the violence in the Central African Republic, Kenya has suffered from attacks by the Somali-based, Islamist terrorist group Al Shabaab, which has damaged inter-community relations.
In April, nearly 150 students were killed in an attack by Shabaab-affiliated gunmen on a university in Garissa, in the northeast of Kenya. In November 2014, more than 20 Christians travelling on a bus near the border with Somalia were taken hostage and murdered by the group, while the 2013 siege of the Westgate Mall in Nairobi left 67 dead.
Security on the Kenyan leg of the trip is expected to be tight, with an estimated 1 million people coming to Nairobi. The government has said it will deploy 10,000 police officers and an additional 10,000 members of the National Youth Service to the capital's streets.
The pontiff will deliver a mass at the University of Nairobi, address young people the city's football stadium, then visit the Kangemi slum to highlight the ongoing blight of poverty in Kenya. Despite the country's economic growth, around 40% of Kenya's population live below the poverty line.
In Uganda, religious leaders have been at the forefront of an often brutal crackdown on homosexuality, which remains illegal in the country. Francis, who has developed a reputation as socially liberal compared to his predecessor, will be under pressure from civil society groups to decry the violence and persecution against the country's LGBT communities, even though he himself has largely stuck to the church's doctrine since becoming pope.