The Humphrey Atherton Papers include two accessions that were arranged independently of one another. Both accessions include the same types of materials and cover the same span of bulk dates. The correspondence and legal papers that pertain to specific cases and individuals are, for the most part, confined within the accessions and do not tend to overlap.

Atherton's papers chronicle his work as an attorney and include legal documents, correspondence from clients and other attorneys, affidavits, copies of depositions, deeds, indentures, leases, wills, and notes. It appears that Atherton was a prominent attorney; his legal receipts give evidence of high fees and household account books and cancelled checks indicate significant spending. His practice seems to have encompassed many types of law and his papers include cases involving real estate, debt, and estate administration. Property lawsuits include an 1810 case involving the seizing of a Spanish ship carrying 500 slaves from an African port. Atherton's work in civil law also extends to divorces and the right of a wife to separate from her husband, as discussed in the 1824 divorce case of John and Diana Mixsell. In addition to handling these isolated cases of high interest, Atherton seems to have had some core clients whose legal needs spanned many years, and in some cases, decades. It is possible to follow the legal woes of some of his clients through several years of correspondence and legal documents.

With the exception of a group of letters from a cousin, his papers do not include personal correspondence, and make but a few veiled references to his private pursuits. Most information about the Athertons' home life can be derived from the expense books and receipts of his wife, Sarah, which provide meager but important insights on the family's lifestyle. Emily Atherton's journals describe the family's travels in the 1830's, but Humphrey Atherton's papers give little other mention of recreation, non-business activities, his early years, or his education.