Lizars's System of anatomical plates was by far his most successful work, going through many editions. The text of the work was originally issued in 12 parts in octavo format, which were then bound together in book form with engraved title; in later editions the text was reset in folio and bound with the plates. There are two issues of parts 2 and 3 of the text in the first edition, the earliest with imprint reading "Printed for Daniel Lizars, 61, Princes Street, Edinburgh; and S. Highley, 174, Fleet Street, London." The later issues' imprint has "Hodges and M'Arthur, Dublin" added at the end; the pagination of the two issues of these parts also varies.

The first edition of the folio atlas illustrating Lizars's System was issued in both uncolored and hand-colored versions, although the 15 plates devoted to the brain and spinal cord are colored in all copies of the first edition. Only a few copies of the first edition of the work were issued with all the plates fully colored.

William Home Lizars's fame as engraver led John James Audubon to engage Lizars to engrave the plates for the double elephant folio Birds of America; however, after Lizars had engraved the first ten plates, he recommended to Audubon that this enormous project (requiring over 76,000 elephant folio hand-colored plates for the 175 copies in the edition) be turned over to Robert Havell in London.