His younger brother John Spottiswood, the historian, became the archbishop of St. Andrews and crowned Charles I. James was educated at home under a tutor, William Strange, and then spent time at Edinburgh grammar school and Linlithgow.
In 1598 he was sent abroad as secretary to the ambassadors to the king of Denmark and the German princes, and on James's accession to the English throne in 1603 Spottiswood was left behind in Scotland in attendance on Queen Anne.
A complex legal case arose when one of Spottiswood's clergy stabbed fatally Lord Balfour's son-in-law Sir John Wemyss, the High Sheriff of Fermanagh in 1626.
[2] Spottiswood published his doctoral thesis, Concio J. Spottiswodii … quam habuit ad Clerum Andreanopoli … pro gradu Doctoratus, Edinburgh, 1616.
He is believed to have been the author of an anonymous manuscript in the Auchinleck library, A Briefe Memoriall of the Life and Death of James Spottiswoode, bishop of Clogher.
It contains information about his early years, but consists mainly of a long account of his private and public troubles as bishop; the last few pages are in another hand, and do not extend to the date of his death.
Spottiswood also published The Execution of Neshech and the Confyning of his brother Tarbith: or a short Discourse shewing the difference betwixt damned Usurie and that which is lawfull.