He took a commission as lieutenant-colonel in the Egyptian Army in 1869, arriving in Egypt in 1870. Serving under Charles Gordon in the southern Sudan, he travelled south to present-day Uganda, signing a treaty with Mutesa I of Buganda. In 1874 he was the second western explorer of Lake Victoria, and the first to discover Lake Kyoga. While on his return journey, he was attacked by the forces of Bunyoro. Further missions of exploration were to the Azande in 1875, and the Juba River in Somalia in 1876. He wrote a book on his adventures, in extravagant style.
In 1875 he commanded Egyptian forces in the McKillop expedition, to the Indian Ocean coast. He resigned his commission in 1877, returned to the United States, and attended Columbia Law School. Subsequently he was a diplomat in Korea, and writer.
His 1884 book The Three Prophets took a very negative line on Charles Gordon. His comments were later taken up by revisionist writers, notably Lytton Strachey in Eminent Victorians. Critics have attacked Chaillé-Long for a lack of accuracy as an author.