James Harrington was the son of Lot Harrington and Sylvia Sage. James' paternal grandfather was Thomas and Freelove Herrington. The maternal grandparent of James were Daniel Sage (1756-1852) and Sybil Jewitt.

Just after James' birth, his mother, Sylvia Sage Harrington died. James was brought up by his Aunt and Uncle, Mr. and Mrs. William Shaw.

James' first wife was Charlotte Walrod. They were married on 22 January 1831, in Allegany County, New York, and moved to Sycamore, Illinois, in June of 1843, where she died in 1871. James then married Mrs. Susan Wyman the following year.

At age 17, he was teaching school and studying medicine during the rest intervals. He then moved to Eagle, New York in 1829, where he practiced medicine until 1831. After their marriage, they moved back to Chenango County, New York, where he practiced medicine until 1843, when he moved to De Kalb County, Illinois, and settled on a homestead four miles from Sycamore, where he and Charlotte had five children.

In 1846 James was a member of the Illinois Legislature and for 9 years was a member of the DeKalb County Board of Supervisors and served the entire period as chairman of the board. He was a member of the Methodist Episcopal Church.

In 1864 he moved to Ann Arbor, Michigan where his two children, Mark Walrod, and Mary attended college. In 1865 he returned to Sycamore, Illinois, and bought property.

The granddaughter of James Harrington and daughter of Nelson Rounds Harrington, Marcia Harrington Westlake wrote a brief biography of James Harrington.

In a letter to Harold Leontine Harrington she stated that "her father was Nelson Rounds Harrington, sixth of the nine children of Dr. James Harrington, who was the son of Lot Harrington and Sylvia Sage, that he (James) was born in Ontario, 20 September 1806, and that his mother died two years later. He (James) was brought up by an uncle and aunt, Mr. and Mrs. William Shaw."

"Marcia Harrington Westlake said that her grandfather (James) practiced medicine in South New Berlin, Chenango County, New York, until 1843, when his health failed and he came to Sycamore, DeKalb County, Illinois, and bought a farm where he lived for twenty years. He was in the state legislature for one term, and lived in Ann Arbor for a time when his younger children were in school there. During the later part of life he conducted a lumber yard in Sycamore. Many of his descendants still live in DeKalb County."

The children of James and Charlotte Walrod Harrington were:
1. Diana Vernon Harrington
2. William Shaw Harrington married Elizabeth Clark. Their daughter, Susan Harrington married Dr. Philp B. Cousland. Their son was Dr. Philip Alexander Clyde Cousland
3. Joseph Harrington
4. George Leach Harrington (Melinda Oakley)
5. Susan Elizabeth Harrington (Ephaim Blake Shurtleff)
6. Mark Walrod Harrington
7. Nelson Rounds Harrington
8. James Franklin Harrington
9. Mary S. Harrington.
James had a half brother by the name of James Harrington. After the death of James' mother, Lot Harrington married Sarah Patterson. Lot and Sarah Patterson had one child, also named James Harrington, who was born in 1811 and died in 1897. James Harrington is buried in the Zion Cemetery, Blissfield, Lenawee County, Michigan.

Dr. James Harrington's son, Mark Walrod Harrington became president of the University of Washington. Mark Walrod Harrington's son was Mark Raymond Harrington. Mark Raymond Harrington was a published archeologist.