Educated in medicine at the University of Edinburgh, Baikie entered the Royal Navy as an assistant surgeon in 1848 and served on several ships as well as on land (1851–54). In 1854 he joined an expedition up the Niger River and, on the death of the ship's captain, took command of the expedition. With a crew made up chiefly of Africans, he explored the Benue River, the main tributary of the Niger, penetrating 250 miles (400 km) farther than any European had before. He published his Narrative of this expedition in 1856.

In 1857, with the rank of consul, Baikie embarked on another Niger expedition, but his steamer was wrecked in rapids. At Lokoja, where the Benue joins the Niger, he founded a trading settlement, where he practiced medicine, compiled African vocabularies, and translated parts of the Bible into the Hausa language. In 1862 he ventured some 250 miles northward to Kano.