Since very little is actually known about the life of Leo, the book fills in the historical episodes, placing him in the company of many of the key historical—political and cultural—figures of his time, including Popes Leo X, Adrian VI, and Clement VII; Ottoman emperors Selim I and Suleiman the Magnificent; Boabdil, the last Moorish king of Granada; Askia Mohammad I of the Songhai Empire; Ferdinand of Spain; Francis I of France; and artist Raphael along with others.

The work explores confrontations between Islam and Christianity as well as the mutual influence that the two religions had on each other and on the people they governed.

The book is based on life experiences that took Leo Africanus almost everywhere in the Islamic Mediterranean, from southern Morocco to Arabia, and across the Sahara.

While filled with biographical hypotheses and historical speculations, the book offers a vivid description of the Renaissance world, with the decline of the traditional Muslim kingdoms and the hope inspired by the Ottoman Empire, as it grew to threaten Europe and restore Muslim unity.

Each section of the book is named after the city that played the major role in Leo's life at a given time: Granada, Fez, Cairo, and Rome.