After his graduation, he spent a year teaching chemistry and physics at Eagleswood Military Academy in Perth Amboy, New Jersey.
[1] After receiving his M.D., Lyons was hired in 1868 by the Detroit College of Medicine (which later would merge with other institutions and become part of what was eventually Wayne State University) as an assistant to Samuel Duffield; the next year Duffield left to found a company that became the drug manufacturer Parke, Davis & Co., and Lyons took his job as the chair of the chemistry department.
In 1888 Lyons was hired as government chemist for the Hawaiian Kingdom; there he also taught chemistry and other scientific subjects at his alma mater Oahu College.
While in Hawaii he made a study of the geology of the islands, published in a number of papers, and collected hundreds of local shells.
After the overthrow of the Hawaiian monarchy Lyons returned to Detroit and in 1898 became supervising chemist and secretary of the pharmaceutical manufacturing firm Nelson, Baker, & Co., a position he held until his death.