He is a Professor of Sociology at the University of Arizona and is a Research Associate with the National Opinion Research Center at the University of Chicago, where he earned his PhD in 1962.

Greeley is the author of over 50 novels and 100 works of non-fiction. His novels have been both popular and controversial, often containing forbidden romances with lurid details of sexual encounters, but typically with a theological underpinning. Greeley's major characters tend to be Irish-American Catholics from Chicago, including a mystery-solving clergyman (first priest, then bishop) named Blackie Ryan who appears in many of Greeley's novels. Bishop Ryan, apparently one of Greeley's alter-egos, is sometimes compared, not always favorably, with G. K. Chesterton's Father Brown.

Greeley's first work of fiction to become a major commercial success was the Cardinal Sins (1981). He then put out the Passover Trilogy, Thy Brother's Wife (1982), Ascent into Hell (1983), and Lord of the Dance (1984). After that, he started putting out 2 or more novels a year. In 1987 alone he produced 4 novels and 2 works of non-fiction. Ostensibly because of the exent of his writing, some of Greeley's critics have accused him of "never having had an unpublished thought."

At the height of the Catholic Church sexual abuse scandal, Greeley put out The Priestly Sins (2004), a novel about a young priest from the Plains States who is exiled to an insane asylum and then to an academic life because he reports abuse that he has witnessed.

Greeley wrote The Making of the Pope 2005, intended as a follow-up to his The Making of the Pope 1978, intended as a first hand account of the coalition building process by which Joseph Ratzinger ascended to the papacy of Benedict XVI In 1996, a Greeley novel, White Smoke, had described the scenario of the election of a new Pope.

Greeley has been an outspoken critic of the George W. Bush administration and the Iraq War.