Anthony's family emigrated to the United States from Britain when he was six. He graduated from Goddard College in Vermont in 1956. He became a naturalized U.S. citizen while serving in the United States Army in 1958. After completing a two year stint in military service, he briefly taught school at Admiral Farragut Academy in St. Petersburg, Florida before becoming a fulltime writer.

Piers Anthony met his future wife, Carol Marble, while both were attending college. They were married in 1956, the same year he graduated from Goddard College, Plainfield, Vermont. After a series of odd jobs Piers Anthony decided to join the U.S. Army in 1957 for a steady source of income and medical coverage for his pregnant wife. He would stay in the Army until 1959; he became a U.S. citizen during this time. While in the army, he became an editor and cartoonist for the battalion newspaper. After leaving the army, he spent a brief stint as a public school teacher before trying his hand at becoming a full-time writer.

Anthony and his wife made a deal...if he could sell a piece of writing within one year, she would continue to work to support him. But if he couldn't sell anything in that year, then he would forever give up his dream of being a writer. At the end of the year, he managed to get a short story published. He credits his wife as the person who made his writing career possible, and he advises aspiring writers that they need to have a source of income other than their writing in order to get through the early years of a writing career.

On multiple occasions Anthony has moved from one publisher to another (taking a profitable hit series with him), when he says he felt the editors were unduly tampering with his work. He has sued publishers for accounting malfeasance and won judgments in his favor. Anthony maintains an Internet Publishers Survey in the interest of helping aspiring writers. For this service, he won the 2003 "Friend of EPIC" award for service to the electronic publishing community. His website won the Special Recognition for Service to Writers award from Preditors and Editors, an author's guide to publishers and writing services.

Anthony invested as an angel investor in Xlibris at one point , and is now a co-owner along with Random House.

Many of his popular novel series have been optioned for movies. His popular series Xanth has a video game, titled "Companions of Xanth" by Legend Entertainment. It is made for PC and on CD-ROM, although it is DOS-based. There is also a board game called Xanth by Mayfair Games.

Piers Anthony's novels usually end with a chapter-long Author's Note, in which he talks about himself, his life, and his experiences as they related to the process of writing the novel. He often discusses correspondence with readers and any real-world issues that influenced the novel. His writings are most similar to novelists such as Steven Brust, Alan Dean Foster and Craig Shaw Gardner.

One important event in Anthony's early literary career was the dispute surrounding the original publication (1976) of But What of Earth?. Editor Roger Elwood commissioned the novel for his nascent science-fiction line Laser Books. As the novel opens, the governments of Earth have just developed the secret of matter transmission ("mattermission"), and the instantaneous transport of matter between points in space without limitation by the speed of light. The book follows college student Scot Krebs as he continues to live on a radically depopulated Earth. Anthony's position in the novel is that as population decreases, technology and civilization go along with it, so Scot and his companions must relearn primitive agriculture while dealing with tribes of hostile nomads.

According to Anthony, he completed But What of Earth? and Elwood accepted and purchased it. Elwood then told Anthony that he wished to make several minor changes and in order not to waste Anthony's time, he had hired copy editor (and author) Robert Coulson to retype the manuscript with the changes. Anthony described Coulson as a friend he had met through science fiction fandom, so he was happy to throw Coulson the work.

However, Elwood told Coulson something entirely different. Coulson understood himself to be a full collaborator, free to make his own significant revisions to Anthony's text, in line with suggestions made by Laser's previous line editors. In exchange, Elwood promised Coulson a 50-50 split with Anthony on all future royalties.

According to Anthony, the published novel is different in many respects from his version: most characters were imagined differently, their motivations revised and often left unclear, much of the dialogue had been reworked, and Coulson had cut many of Anthony's scenes and added several of his own invention. In Anthony's view, Coulson's efforts completely changed the tenor of the work, and not for the better.

Laser's ultimate publication of But What of Earth? listed Anthony and Coulson together as collaborators. Publication rights were reverted to Anthony under threat of legal action. Laser folded the next year, in 1977.

In 1989, Anthony (re)published his original But What of Earth? in an annotated edition through Tor Books. This edition contains an introduction and conclusion setting out the story of the novel's permutations and roughly 60 pages of notes by Anthony giving examples of changes to plot and characters, and describing some of the comments made by copy editors on his manuscript.

Anthony currently lives with his wife on a tree farm which he owns in Florida. He and his wife had two daughters, Penny and Cheryl, and have one grandchild, Logan.

On September 3, 2009, their daughter Penelope "Penny" Carolyn Jacob died from apparent respiratory paralysis following surgery for melanoma which had metastasized to her brain. She is survived by her husband and her daughter Logan.

For autobiography refer to autobiographical subsection.