Rachels was born in Columbus, Georgia, and graduated from Mercer University in 1962. He received his Ph.D. in 1967 from the University of North Carolina, Chapel Hill, studying under Professors W. D. Falk and E. M. Adams. He taught at the University of Richmond, New York University, the University of Miami, Duke University and the University of Alabama at Birmingham, where he spent the last twenty-six years of his career. He married Carol Williams in 1962, and they had two sons, David and Stuart. He died of cancer in 2003 in Birmingham, Alabama.

Over the course of his career, Rachels wrote six books and 85 essays, edited seven books and gave some 275 professional lectures. His work has been translated into Dutch, Korean, Spanish, Italian, Japanese, Indonesian, Icelandic, Portuguese, Chinese, Swedish and Serbo-Croatian.

Rachels has argued for moral vegetarianism and animal rights, preferential quotas, the humanitarian use of euthanasia and the idea that parents should give as much fundamental moral consideration to another's children as they do to their own. Later in his career, Rachels realised that a lifetime of analysing specific moral issues had led him to adopt the general ethic of utilitarianism, according to which actions are assessed by their effects on both human and nonhuman happiness.

Rachels's best-known work is The Elements of Moral Philosophy. It went to its sixth edition in 2009, having been revised by Rachels's son, Stuart Rachels. Among the subjects covered are ethical and simple subjectivism, emotivism, as well as ethical and psychological egoism, to name but a few. The text uses real-world examples to highlight points regarding complicated philosophical principles. Rachels had a history of using such examples. The publication in 1971 of his anthology Moral Problems marked a shift from teaching meta-ethics in American colleges to teaching concrete practical issues. Moral Problems sold 100,000 copies over three editions.

In 1975, Rachels wrote "Active and Passive Euthanasia", which originally appeared in the New England Journal of Medicine and argued that the distinction so important in the law between killing and letting die has no rational basis. Rachels claims that, if we allow passive euthanasia, we should also allow active euthanasia. He supports this claim with two more:

1. Active euthanasia is more humane than passive euthanasia; and
2. killing versus letting die makes no moral difference in itself.

"The End of Life" (1986), a moral treatise on life and death, broadened and deepened these ideas.

Rachels wrote only a few works that were not directly focussed on ethics. Created from Animals (1990) made the case that a Darwinian world-view has widespread philosophical implications, including drastic implications for our treatment of nonhuman entities. Can Ethics Provide Answers? (1997) was Rachels's first collection of papers. His second, The Legacy of Socrates, was published posthumously in 2007. Shortly before his death, he wrote Problems from Philosophy, an introduction to philosophy. This book was published posthumously in 2005 and revised by his son Stuart in 2008.