Born in New York City, Sobol is the son of Ira J. and Ida (Gelula) Sobol. Donald attended the NYC Ethical Culture Fieldston School and graduated from the Fieldston School in New York City in 1942. Sobol served with the Army Corps of Engineers during World War II and served in the Pacific Theater. Following the war, he attended Oberlin College, where he earned a bachelor's degree. He also attended the New School of Social Research.

He started his professional career as a copy boy for the New York Sun, eventually working his way up to reporter. In 1949, he took a job at the New York Daily News, and worked there for two years. After a brief stint as a buyer at Macy's in New York, he moved to Florida and started writing full time.

He started writing the syndicated series Two-Minute Mysteries in 1959, starring criminologist Dr. Haledjian. It proved very popular and ran for more than ten years. In 1963, he started writing the Encyclopedia Brown series, featuring amateur sleuth Leroy "Encyclopedia" Brown. Compared to Two-Minute Mysteries which features crimes as serious as murder, the Encyclopedia Brown books are more juvenile-oriented, often deal with matters such as pranks or petty theft. Sobol's Encyclopedia Brown titles have never been out of print and have been translated into twelve languages. In 1975, the Mystery Writers of America honored Sobol and his Encyclopedia Brown series with a Special Edgar Award. In 2007, Sobol released a new Encyclopedia Brown book, Encyclopedia Brown Cracks The Case.

Sobol also wrote the children's novel Secret Agents Four, in which a group of Miami teenagers attempt to thwart foreign saboteurs.

Sobol has written more than 65 books. In addition to the books he has written for children, Sobol has also written a number of nonfiction books on topics ranging from history to investing. He has also written and contributed to magazines under a variety of pen names. His manuscripts are stored at the University of Minnesota, in the Kerlan Collection.

Encyclopedia Brown series

The Encyclopedia Brown books, in order of publication (parenthesis indicate numbers on original release cover art):

1. (1) Encyclopedia Brown, Boy Detective (1963, ISBN 0-525-67200-1, 1982 reissue ISBN 0-553-15724-8)
2. (2) Encyclopedia Brown Strikes Again (the Case of the Secret Pitch) (1965, ISBN 0-590-01650-4, second title reissue ISBN 0-525-67202-8)
3. (3) Encyclopedia Brown Finds the Clues (1966, ISBN 0-525-67204-4)
4. (4) Encyclopedia Brown Gets His Man (1967, ISBN 0-525-67206-0)
5. (5) Encyclopedia Brown Solves Them All (1968, ISBN 0-525-67212-5)
6. (6) Encyclopedia Brown Keeps The Peace (1969, ISBN 0-525-67208-7)
7. (7) Encyclopedia Brown Saves the Day (1970, ISBN 0-525-67210-9)
8. (8) Encyclopedia Brown Tracks Them Down (1971, ISBN 0-553-15721-3)
9. (9) Encyclopedia Brown Shows the Way (1972, ISBN 0-553-15142-X)
10. (10) Encyclopedia Brown Takes the Case (1973, ISBN 0-553-15723-X)
11. (11) Encyclopedia Brown Lends a Hand (1974, ISBN 0-553-48133-9, reissued as Encyclopedia Brown and the Case of the Exploding Plumbing and Other Mysteries, ISBN 0-590-44093-4)
12. (12) Encyclopedia Brown and the Case of the Dead Eagles (1975, ISBN 0-590-43343-1)
13. (13) Encyclopedia Brown and the Case of the Midnight Visitor (1977, ISBN0-553-15586-5)
14. (14) Encyclopedia Brown Carries On (1980, ISBN 0-02-786190-2)
15. (15) Encyclopedia Brown Sets the Pace (1981, ISBN 0-02-786200-3)
16. (15½) Encyclopedia Brown Takes the Cake (1982, ISBN 0-590-07843-7) (Co-written with Glenn Andrews)
17. (16) Encyclopedia Brown and the Case of the Mysterious Handprints (1985, ISBN 0-553-15739-6)
18. (17) Encyclopedia Brown and the Case of the Treasure Hunt (1988, ISBN 0-553-15650-0)
19. (18) Encyclopedia Brown and the Case of the Disgusting Sneakers (1990, ISBN 0-688-09012-5)
20. (19) Encyclopedia Brown and the Case of the Two Spies (1995, ISBN 0-385-32036-1)
21. (20) Encyclopedia Brown and the Case of Pablo's Nose (1996, ISBN 0-385-32184-8)
22. (21) Encyclopedia Brown and the Case of the Sleeping Dog (1998, ISBN 0-385-32576-2)
23. (22) Encyclopedia Brown and the Case of the Slippery Salamander (2000, ISBN 0-385-32579-7)
24. (23) Encyclopedia Brown and the Case of the Jumping Frogs (2003, ISBN 0-385-72931-6)
25. (24) Encyclopedia Brown Cracks the Case (2007, ISBN 978-0-525-47924-6)