A large proportion of the book contains detailed information on the domestication of animals and plants but it also contains in Chapter XXVII a description of Darwin's theory of heredity which he called pangenesis.

Darwin had been working for two years writing his "big book", provisionally titled Natural Selection, when on 18 June 1858 he received a parcel from Alfred Wallace, who was then living in Borneo.

In his accompanying letter Darwin wrote "It is a very rash & crude hypothesis yet it has been a considerable relief to my mind, & I can hang on it a good many groups of facts.

"[10] Huxley pointed out the similarities of pangenesis to the theories of Georges Louis Leclerc, Comte de Buffon, and the Swiss naturalist Charles Bonnet but eventually wrote encouraging Darwin to publish: "Somebody rummaging among your papers half a century hence will find Pangenesis & say 'See this wonderful anticipation of our modern Theories—and that stupid ass, Huxley, prevented his publishing them'".

At the end of January he wrote to Murray: "I feel a full conviction that my Chapter on man will excite attention & plenty of abuse & I suppose abuse is as good as praise for selling a Book"[15] but he then apparently decided against the idea for a week later in a letter to his close friend Joseph Hooker he explained "I began a chapter on Man, for which I have long collected materials, but it has grown too long, & I think I shall publish separately a very small volume, 'an essay on the origin of mankind'".

[14] The Variation of Animals and Plants Under Domestication went on sale on 30 January 1868, thirteen years after Darwin had begun his experiments on breeding and stewing the bones of pigeons.

These arguments, as well as many others, use the vast amount of data Darwin gathered about dogs and cats to support his overarching thesis of evolution through natural selection.

He then goes on to make similar points regarding horses and donkeys, sheep, goats, pigs, cattle, various types of domesticated fowl, a large number of different cultivated plants, and, most thoroughly, pigeons.

[25] In the final pages of the book Darwin directly challenged the argument of divinely guided variation advocated by his friend and supporter the American botanist Asa Gray.

He used the analogy of an architect using rocks which had broken off naturally and fallen to the foot of a cliff, asking "Can it be reasonably maintained that the Creator intentionally ordered ... that certain fragments should assume certain shapes so that the builder might erect his edifice?

"[26] In the same way, breeders or natural selection picked those that happened to be useful from variations arising by "general laws", to improve plants and animals, "man included".

[27] Darwin confided to Hooker "It is foolish to touch such subjects, but there have been so many allusions to what I think about the part which God has played in the formation of organic beings, that I thought it shabby to evade the question.

[35][36] De Vries in 1889 praised the "masterly survey of the phenomena to be explained" and accepted the idea that "the individual hereditary qualities of the whole organism are represented by definite material particles".

[37][38] In a similar vein, Weismann in his 1893 work Germ-Plasm said "although Darwin modestly described his theory as a provisional hypothesis, his was, nevertheless, the first comprehensive attempt to explain all the known phenomena of heredity by a common principle ... [I]n spite of the fact that a considerable number of these assumptions are untenable, a part of the theory still remains which must be accepted as fundamental and correct,--in principle at any rate,--not only now but for all time to come.