Sereno Watson was born on December 1, 1826, in East Windsor Hill, Connecticut.

He was a botanist. He graduated from Yale University in 1847. He worked as a tutor at Iowa College from 1852 to 1854. In 1866, he entered the Sheffield Scientific School of Yale University and pursued the studies of chemistry and mineralogy. In 1867, he joined the Clarence King Expedition in California and eventually became the expedition botanist. Although he had no prior botanical training, Watson wrote the "Botany of the King Expedition" (1871). Asa Gray appointed him an assistant in the Gray Herbarium and Botanical Garden of Harvard University in 1873. In 1874, he became its curator, a position he held until his death. In 1881, he was appointed instructor in phytogeography. Watson was elected a Fellow of the American Academy of Arts and Sciences in 1874 and a member of the National Academy of Sciences in 1889. He received an honorary Ph.D. degree from Iowa University. He contributed many articles to the Proceedings of the American Academy of Arts and Sciences.

He died unmarried on March 9, 1892, in Cambridge, Massachusetts.