Born the son of a schoolmaster at Frankfurt in Germany, Engelmann was educated at the universities of Heidelberg, Berlin, and Würzburg where he obtained his MD in 1831. In the following year he visited America to invest in some land for a wealthy uncle and decided in 1835 to settle and practice medicine in St. Louis.

Engelmann was not only a plant collector of some importance; he also did much to initiate and organize major collecting expeditions of the flora of the West. It was thus through Engelmann that many of the newly collected specimens passed on their way to eastern scholars as Asa Gray at Harvard. Engelmann's role became more official with the setting up of the Missouri Botanical Garden in 1859 with the backing of the St. Louis businessman Henry Shaw.

He is also remembered for his demonstration that some stocks of American vine were resistant to the pest Phylloxera, which had begun to devastate the vineyards of Europe from 1863 onward.