After graduating, Pennypacker practiced medicine in Philadelphia for a time before moving back to Chester County and practicing medicine there.[1] He then worked as an assistant superintendent and manager of the Phoenixville Iron Works for two years. In 1849, he became a superintendent at Durham Iron Works in Durham Township in Bucks County. He worked there for one year before resigning due to poor health. He then returned to Chester County and purchased a farm and worked the land. He owned a 176 acres (71 ha) farm and a grist mill.[1]
Pennypacker married Annie R. Walker, daughter of William Walker, of Tredyffrin Township on April 27, 1848. They had five sons and four daughters, including William H., Matthias A., Sarah, Mary Athalia, Isaac A. and Annie W. His wife died in 1868. In 1878, he married Kate A. Cook, daughter of Tillinghast J. Cook, of Parkersburg, West Virginia. They had one son, James C.[1][3] He was a member of the Methodist Episcopal Church in Phoenixville.[1] His nephew was Pennsylvania Governor Samuel W. Pennypacker.[3]
Pennypacker died on August 31, 1899, at his home in Schuylkill Township. He was buried at Morris Cemetery.[4][5]
