Nachtigal, the son of a Lutheran pastor, was born at Eichstädt in the Province of Saxony. After medical study at the universities of Halle, Würzburg and Greifswald, he practised for a few years as a military surgeon. Finding the climate of his native country injurious to his health, he went to Algiers and Tunis, and took part, as a surgeon, in several expeditions into the interior.
Commissioned by King William I of Prussia to carry gifts to Umar of Borno in acknowledgment of kindness shown to German travellers, he set out in 1869 from Tripoli, and succeeded after two years journeyings in accomplishing his mission. During this period he visited Tibesti and Borku, regions of the central Sahara not previously known to Europeans. From Bornu he went to Bagirmi, and, proceeding by way of Wadai and Kordofan, emerged from darkest Africa, after having been given up for lost, at Khartum in the winter of 1874. His journey, graphically described in his Sahara und Sudan (3 vols., 1879-1889), placed the intrepid explorer in the front rank of discoverers.
On the establishment of a protectorate over Tunisia by France, Nachtigal was sent thither as consul-general for the German Empire, and remained there until 1884, when he was dispatched by Prince Otto von Bismarck to West Africa as special commissioner, ostensibly to inquire into the condition of German commerce, but really to annex territories to the German flag, before the British did. As the result of his mission Togoland and Kamerun were added to the German colonial empire. On his return voyage he died at sea off Cape Palmas on April 20, 1885, and was buried at Grand Bassam.
Nachtigal remains the other great German explorer in Africa, second only to Heinrich Barth (1821–1865). Like his predecessor, Nachtigal was mainly interested in ethnography and additionally in tropical medicine. His works stand out because of their wealth of details and above all because of the traveller's unbiased views on Africans. In contrast to most contemporary explorers he did not believe in the alleged inferiority of Africans, which is clearly reflected in his descriptions and even in his choice of words. He had witnessed slave hunts performed by African rulers and the cruelties inflicted on other Africans. The horror that he felt about these atrocities made him enter the colonial service because he naively believed that European domination of Africa might stop slave hunting and slave keeping.