The work gives a short guide to every Shakespeare play, as well as two epic poems. Asimov organizes the plays not in the usual way – as tragedies, comedies, and histories – but regionally, as follows:

• Greek
• Roman
• Italian
• English

The last two categories are treated broadly; 'Italian' applies to neighbouring countries, and both Hamlet and Macbeth are listed with 'The English Plays'. Asimov gives a detailed justification for doing this.

Within each category, the plays are arranged according to internal (historical) chronology, making allowance for the several not based on actual events. Asimov notes how much is real history, and describes who the historical people were, where applicable. He traces those characters who appear in more than one play, and provides maps to explain key geographical elements.

Asimov's approach is not popular with some readers' prejudices:

Fans of Asimov's science-fiction generally have little taste for door-stopper books such as Asimov's Guide to Shakespeare or The Shaping of England, and specialists are never happy to see clever outsiders make hay in their fields.

— Peter Temes^[1]

Asimov's Guide to Shakespeare, vols I and II (1970), ISBN 978-0-517-26825-4. Gramercy Books.

Nearly 800 pages long plus an index, the work was originally published in two volumes; Greek, Roman and Italian in the first and 'The English Plays' in the second.

Asimov dedicated the work to his late father, Judah Asimov.

• Isaac Asimov bibliography (chronological)

• Meserole, Harrison T.; Smith, John B. (1980). "Shakespeare: Annotated World Bibliography for 1979: Reference Works". Shakespeare Quarterly. 31 (4). Folger Shakespeare Library: 492–93. doi:10.1093/sq/31.4.468. eISSN 1538-3555. ISSN 0037-3222. JSTOR 2869590.
• Temes, Peter (15 March 2002). "100 Words a Minute, But Finally Stopped by AIDS". Forward. Archived from the original on 7 March 2003. Retrieved 25 March 2017.