- Proprietor of Manhattan's Mysterious Bookshop, which celebrated its 30th anniversary on April 13, 2009
- Publisher of The Armchair Detective, the Edgar-winning quarterly journal devoted to the study of mystery and suspense fiction, for seventeen years
- Founder and publisher of The Mysterious Press
- Creator of publishing firms Otto Penzler Books and The Armchair Detective Library
- Series Editor of The Best American Mystery Stories of the Year at Houghton Mifflin
- He is also the co-Series Editor (with Thomas H. Cook) of the annual Best American Crime Reporting (Ecco/HarperCollins)
- Editor of his own imprints at Houghton Mifflin Harcourt in the U.S. and Atlantic Books in the U.K.
- "The Crime Scene" columnist for The New York Sun for five years
- Writer of a number of mysteries
Over the years, Penzler has won numerous awards from the Mystery Writers of America, including the Ellery Queen Award (for his exceptional contributions to mystery publishing), and more than one Edgar® Award (1977 for his Encyclopedia of Mystery and Detection; in 2010 for The Lineup: The World's Greatest Crime Writers Tell the Inside Story of Their Detectives.) and the Raven Award (for his work as owner of the Mysterious Bookshop).