In 1958, McPherson began his professional career as a copy boy for the Washington Post, becoming a staff writer a few months later.

Russell Banks wrote in the New York Times Book Review, "William McPherson's first novel is an extraordinarily intelligent, powerful and, I believe, permanent contribution to the literature of family, childhood and memory.

McPherson also contributed to The New Republic, The Nation, The New Yorker, the International Herald Tribune, and Life, among other periodicals.

In 2014, McPherson wrote about how he was living in relative poverty,[8] after spending his inheritances and losing money in the stock market.

[9] McPherson died March 28, 2017, at a hospice center in Washington of complications from congestive heart failure and pneumonia.