[1] As president of the Franklin Institute in Philadelphia, Pennsylvania, Sellers proposed the adoption of a system of screw threads which was easier for ordinary mechanics and machinists to cut than a similar design by Joseph Whitworth.

[2] His cousins include George Escol Sellers (1808–1899), an inventor holding patents for a hill-climbing locomotive, a pulp-paper process, converting steamboats to coal, and removing brine from salt water, and Coleman Sellers II (1827–1907), a five-term president of the Franklin Institute, who was instrumental in harnessing Niagara Falls for electricity.

After receiving a private education in a family-run school, he began apprenticing at age fourteen with his uncle, J. Morton Poole, in a machine shop near Wilmington, Delaware.

Returning to West Philadelphia to start his own machine company, he eventually formed a partnership with his brother-in-law Edward Bancroft (1811–1855) in 1848.

At a meeting on September 15, 1864, he presented a uniform system of screw threads which with its angle and its flat top and bottom differed from Whitworth's British standard.