Dr. Jeremiah Spofford Jr. was born on December 8, 1787, in New Rowley (now Georgetown), the son of Jeremiah and Temperance (Spofford) Spofford. After a course of medical studies under Drs. Whiton and Parkhurst of Winchendon, Massachusetts, Spofford was licensed to practice medicine in June 1813. In 1817, he moved to Bradford (to a section of the town which is now Groveland) to assume the medical practice of the deceased Dr. Ebenezer Jewett. Spofford practiced medicine in that place for the next fifty-four years. During that time he was a member of the Massachusetts Medical Society and the Essex North District Medical Society.

In addition to his medical profession, Spofford was an educator. In 1810 and 1811 he served as a schoolmaster in New Rowley, and in 1821 he was a founder of the Merrimack Academy in Bradford, an institution that he remained affiliated with until at least 1872. Throughout his working life, Spofford lectured at Merrimack Academy and in front of school and civic groups across Essex County on politics, history, science, and philosophy. From 1821 until 1880 Spofford was connected with the Haverhill Gazette in several capacities, including part-time owner, editor, and columnist. In another business venture he was involved with two partners (William Balch and Nathaniel Ladd) in a real estate enterprise that dissolved in a financial dispute over rents owed and interest due on notes. The legal dispute, called the "Corporation Case," lasted from 1853 to 1855 and was finally removed from the courts and resolved in an ecclesiastical council of the local church. Spofford also held posts in local government and was active in enhancing railroad and steamship service to towns of western Essex County. Spofford's political leanings evolved from Federalist, to Whig, to Republican (as the political parties realigned and changed). In 1838 and 1839 he represented the region in the Massachusetts Senate.

The study of local and family history occupied Spofford's leisure time. He collected data on the Spofford family and authored A Family Record of the Descendants of John and Elizabeth, His Wife (Haverhill: E. G. Frothingham, 1851 and 1869). The book was updated and expanded by his daughter Aphia, and republished as Aphia Spofford, editor, A Genealogical Record [of the] Descendants of John Spofford and Elizabeth Scott by Dr. Jeremiah Spofford, Jr. (Boston: Alfred Mudge and Son, 1888).

On September 14, 1813, Spofford married his second cousin, Mary Ayer Spofford (1789-1876), the daughter of Eleazer and Mary (Flint) Spofford of Jaffrey, New Hampshire. The newly married couple resided in Hampstead, New Hampshire, for three years and then moved to Bradford (now Groveland), Massachusetts, where they resided for the remainder of their lives. The couple had nice children: Laura Ayer Spofford (1814- ), Charles Whiton Spofford (1816- ), Charlotte Eustis Spofford (1819-1888), Hershel Ainsworth Spofford (1825-1904), Mary Putnam Spofford (1823-1856), Cecilia Peabody Spofford (1826-1886), Morris Spofford (1829-1884), Lucy Tenney Spofford (1831-1833), and Aphia Tenney Spofford (1834- ). This collection also includes papers of members of the extended Spofford family of Essex County. The bulk of these are papers that document the lives and descendants of three sons of John Spaffard/Spofford (1678-1735) and his two wives, Dorcas Hopkinson (1676- ) and Sarah Poor. Those sons are Abner, Daniel, and Eliphalet Spofford.

The first son of John Spaffard/Spofford represented in this collection, Abner Spofford (1705-1777), was a millwright of Georgetown. Abner's son, Eleazer Spofford (1739-1828), was a millwright and road-builder of Georgetown and Bradford, Massachusetts, and Jaffrey, New Hampshire. Abner's great-grandson, Ainsworth Rand Spofford (1751-1872) of Cincinnati, Ohio, and Washington, D. C., served as Librarian of Congress from 1864 to 1897.

The second son of John Spaffard/Spofford, Daniel Spofford (1721-1803), was an architect and builder of Georgetown and served as a colonel in the Essex County militia during the American Revolution. Daniel's son, Moody Spofford Sr. (1744-1828), was an architect of Georgetown who served as a lieutenant during the Revolution. Moody Sr.'s son, Moody Spofford Jr. (1776- ), was of Georgetown also. Another son of Daniel, Amos Spofford (1751-1805), was a physician of Georgetown from 1771 to 1805. Amos's sons (and Daniel's grandsons), Moses Dole Spofford (1773-1832) of Georgetown and Richard S. Spofford (1787-1872) of Newburyport, were physicians.

The third son of John Spaffard/Spofford, Eliphalet Spofford (1725-1776), of Georgetown, Massachusetts, and Charlestown, New Hampshire, was a captain in the American Revolution who died of fever during the war. Eliphalet's daughter, Eunice (Spofford) Hale (1794-1847), was the wife of Johnathan Hale of Groveland. Eliphalet's granddaughter (through his daughter Lucy [Spofford] Adams), Elizabeth "Betsey" (Adams) Chapman (1794-1847), was the wife of Eliphaz Chapman of Gilead, Maine.

The collection also includes papers of Abraham Spofford (1717- ), an Essex County cousin of the Spoffords described above, and an unidentified Ebenezer Spofford.