Jacoby, who began her career as a reporter for The Washington Post, has been a contributor to a wide variety of national publications, including The New York Times, the Los Angeles Times, The American Prospect, Mother Jones, The Nation, Glamour, and the AARP Bulletin and AARP Magazine. She is currently a panelist for "On Faith," a Washington Post-Newsweek blog on religion. As a young reporter she lived for two years in the USSR.

Her book Freethinkers: A History of American Secularism was named a notable book of 2004 by The Washington Post and The New York Times. It was also named an Outstanding International Book of the Year by the Times Literary Supplement (London) and The Guardian. Wild Justice: The Evolution of Revenge (1984) was a finalist for the Pulitzer Prize.

Her book Half-Jew: A Daughter's Search for Her Family's Buried Past (2000) explores her partial Jewish roots. Raised in a Roman Catholic home, Jacoby did not learn of her father's Jewish roots until she was in her early 20s.

Jacoby has argued that the idea of anti-Catholicism being a significant force in American life today is a canard, perpetrated by theologically and politically right-wing Roman Catholics and aimed at anyone who stands up to the Church's continuing attempts to impose its values on all Americans.

She is currently a member of the advisory board of the Secular Coalition for America, a national lobbying organization representing the interests of secular Americans.