[5] Lightman began his career studying Victorian agnosticism amongst prominent scientific naturalists, including such figures as Thomas Henry Huxley and John Tyndall, producing the book The Origins of Agnosticism: Victorian Unbelief and the Limits of Knowledge published in 1987.

The focus of this work was on the ways in which early agnostics did not simply see their agnosticism as a mask for atheism, but instead arrived at agnosticism via a questionable understanding of the philosophy of knowledge of the German philosopher Immanuel Kant, as that philosophy was introduced into Britain by Henry Longueville Mansel.

[6][7][8] Since 1989, Lightman's work has largely focused on the popularization of science and particularly on the role that Victorian non-professional periodicals and print culture played in shaping the form of scientific debates in the public arena.

[13] Lightman was editor-in-chief of the journal Isis from 2004-2014 and served as president of the History of Science Society 2018–2019.

[3] At York University, Lightman has been appointed to a number of administrative positions over the years, including associate dean of arts, acting director of academic staff relation, coordinator of the interdisciplinary program science and society, and director of the graduate program in humanities.