One of five children, Powers was born in Evanston, Illinois. His family later moved a few miles south to Lincolnwood where his father was a local school principal. When Powers was 11 they moved to Bangkok, Thailand, where his father had accepted a position at International School Bangkok, which Powers attended through his freshman year, ending in 1972. During that time outside the U.S. he developed skill in vocal music and proficiency in cello, guitar, saxophone, and clarinet. He also became an avid reader, enjoying nonfiction, primarily, and classics such as the Iliad and the Odyssey.
The family returned to the U.S. when Powers was 16. Following graduation in 1975 from DeKalb High School in DeKalb, Illinois, he enrolled at the University of Illinois at Urbana-Champaign (UIUC) with a major in physics, which he switched to English literature during his first semester. There he earned the BA in 1978 and the MA in Literature in 1980. He decided not to pursue the PhD partly because of his aversion to strict specialization, which had been one reason for his early transfer from physics to English, and partly because he had observed in graduate students and their professors a lack of pleasure in reading and writing (as portrayed in Galatea 2.2).
For some time Powers worked in Boston, as a computer programmer. Viewing the 1914 photograph "Young Farmers" by August Sander, on a visit to the Museum of Fine Arts, he was inspired to quit his job and spend the next two years writing his first book, Three Farmers on Their Way to a Dance, which was published by William Morrow in 1985. It comprises three alternating threads. The first is a novella featuring the three young men in the photo during World War I. The second features a technology magazine editor who is obsessed with the photo. The third is the author's critical and historical musings, mainly about the mechanics of photography and the life of Henry Ford.
Powers moved to the Netherlands, where he wrote Prisoner's Dilemma, a work that juxtaposes Disney and nuclear warfare. He followed this with The Gold Bug Variations, a story that ties together genetics, music, and computer science. Powers has said that he moved to the Netherlands to avoid the publicity and attention generated by his first novel.
The Time of Our Singing (2003) is a story about the musician children of an interracial couple who met at Marian Anderson's legendary concert on the steps of the Lincoln Memorial in 1939. Powers displays his knowledge of music and physics in this exploration of race relations and the burdens of talent.
Powers's ninth novel, The Echo Maker (2006), won a National Book Award and was a Pulitzer Prize for Fiction finalist. The novel tells the story of a young man whose brain is injured in a truck accident. Although he largely recovers, he has cognitive impairments, including Capgras syndrome, the suspicion that his sister has been replaced by an impostor. Another important character is a consulting neurologist, modeled to some degree on Oliver Sacks and perhaps Gerald Edelman. The novel explores the themes of cognitive construction of reality, and the relationships between memory and emotional bonds between people, and some of the tensions between the beneficial and exploitative aspects of a famous doctor's work. The events occur along the Platte River in Nebraska, near the shrinking migratory refuge of the sandhill cranes. Social frictions in the story arise out of water and land use disputes.
Powers's tenth novel, Generosity: An Enhancement, was published on September 29, 2009. It features a writing instructor named Russell Stone, who encounters one of his students, Thassa, an Algerian woman who is constantly happy. Meanwhile, journalists and scientists hope to exploit Thassa's joyfulness for financial gain.
In 2010 and 2013, Powers was a Stein Visiting Writer at Stanford University, during which time he partly assisted in the lab of biochemist Aaron Straight.
Powers's most recent novel, Orfeo, was published January 20, 2014. Peter Els, a retired music composition instructor and avant-garde composer, is mistaken for a bio-terrorist after being discovered with a makeshift genetics lab in his house.
Powers has stated that his next novel is to be about trees.
Powers was named a MacArthur Fellow in 1989. He received a Lannan Literary Award in 1999. He currently teaches a graduate course in multimedia authoring, as well as an undergraduate course on the mechanics of narrative, at UIUC, where he is the Swanlund Professor of English.
On August 22, 2013, Stanford University announced that Powers had been named the Phil and Penny Knight Professor of Creative Writing in the Department of English.
Reviewer William Deresiewicz has written critically of Powers's oeuvre; in his review of The Echo Maker, he writes of The Gold Bug Variations that "what's missing from the novel is, well, a novel. The characters are idealized, the love stories mawkish and clichéd, the emotions meant to ground the scientific speculations in lived experience announced rather than established. The thinnest of devices are introduced to allow Powers to suspend the plot for dozens of pages at a stretch." But Deresiewicz also noted that his "is hardly the standard view of Powers's work. Over the past two decades, Powers has established himself as one of our most praised as well as one of our most prolific writers of fiction."
In an admiring essay, Canadian novelist Margaret Atwood praised The Echo Maker as "a grand novel—grand in its reach, grand in its themes, grand in its patterning. That it might sometimes stray over the line into the grandiose is perhaps unavoidable: Powers is not a painter of miniatures. Of the two extremes of American mannerist style, the minimalist or Shaker chair (Dickinson, Hemingway, Carver) and the maximalist or Gilded Age (Whitman, James, Jonathan Safran Foer), Powers inclines toward the latter. He gets his effects by repetition, by a Goldberg Variation–like elaboration of motifs, by cranking up the volume and pulling out all the stops".