He rose through the ranks and eventually worked as cashier (second in charge) at the Bank of Chester County from November 1, 1857, to June 3, 1883, succeeding David and Washington Townsend.

Notably, he settled the affairs of West Chester's Bank of Brandywine, which opened its doors in 1871 and failed in 1875 due to the Panic of 1873.

He accepted the position of curator in charge of the William S. Vaux Collection of mineral specimens and archaeological artifacts at the Philadelphia Academy of Natural Sciences,[2] of which he was elected a member in 1882.

[8] He was married to Elmira Cherrington (1818–1881) and had four children: Emma Clara, Alonzo Potter, William Alger, and Elsie Louise.

[9] After picking up his first mineral specimen in 1837, Jefferies joined the Cabinet of Natural Science (West Chester's scientific organization), befriended leading naturalists in the area such as William Darlington and Lewis White Williams, and collected mineral specimens from the quarries and mines of the region.

Notable U.S. correspondents included Benjamin Silliman, George Brush, and James Dana, to whose System of Mineralogy he contributed specimens for illustration.

[2][15] In addition to his collecting activities, Jefferis taught mineralogy for one year at the West Chester State Normal School while continuing to work at his bank.