Charles Sheffield attended St. John's College Cambridge where he graduated with a Double First in Mathematics and Physics. During his studies he met and later married his first wife, Sarah Sanderson, whose death in 1977 was the catalyst for his writing career. The two of them had a son, Charles Christopher, and his first daughter, Ann Elizabeth. The family soon after moved to America where Sheffield began working in the field of practical physics, a career that would lead him to a consultancy with NASA and the role of chief scientist at the Earth Satellite Corporation in Washington.

In response to the traumatic grief from the death of his wife Sarah to cancer (in 1977), he began what would become a stellar career in the field of science fiction, winning both the prestigious Nebula and Hugo awards and serving as President of the Science Fiction and Fantasy Writers of America (1984—1986). He maintained two successful careers, consulting for various scientific corporations while earning fame for his "Hard SF". Sheffield was known to note that "the world was really too interesting to let alone." During this period he lived in Washington, DC, and met and married Linda Zall, a fellow scientist, and had two daughters, Elizabeth Rose and Victoria Jane.

At the time of his death, he was married to writer Nancy Kress, and living with his children in Silver Spring, MD.

Novels

• The Web Between The Worlds (1979)
• My Brother's Keeper (1982, revised 1998)
• The Selkie (1982) (with David Bischoff)
• The McAndrew Chronicles (1983) - A collection of stories, partially sequel to The Web Between The Worlds
• Between the Strokes of Night (1985)
• The Nimrod Hunt (1986, revised as The Mind Pool, 1993)
• Trader's World (1988)
• Brother to Dragons (1992) - Won the John W. Campbell Memorial Award
• Cold as Ice (1992)
• Godspeed (1993)
• The Mind Pool (1993)
• The Judas Cross (1994) - With David Bischoff
• The Ganymede Club (1995)
• Higher Education (1995)
• The Billion Dollar Boy (1997)
• Putting Up Roots (1997)
• Tomorrow and Tomorrow (1997)
• Aftermath (1998)
• The Cyborg from Earth (1998)
• Starfire (1999)
• The Spheres of Heaven (2001)
• Dark as Day (2002)
• The Amazing Dr. Darwin (2002)

The Proteus Universe

• Sight of Proteus (1978)
• Proteus Unbound (1989)
• Proteus in the Underworld (1995)

The Heritage Universe

• Summertide (1990) (Book One)
• Divergence (1991) (Book Two)
• Transcendence (1992) (Book Three)
• Convergence (1997) (Book Four)
• Resurgence (2002) (Book Five)

Non-fiction

• The Borderlands of Science (1999)

Collections

• Vectors (1979)
• Hidden Variables (1981)
• Georgia On My Mind and Other Places (1995)
• The Compleat McAndrew (2001)

Short stories

• "Humanity Test" (1989)
• "The Double-Spiral Staircase" (1990?)
• "A Braver Thing" (1990)
• "Georgia on My Mind" (1993) (Hugo, Nebula)
• "Tunicate, Tunicate, Wilt Thou Be Mine" (1989)
• "Dies Irae" (1985)
• "Brooks Too Broad For Leaping" (1998)
• "The Diamond Drill" (2002)