J. Francis McComas, reviewing the American release for The New York Times, declared that the "outstanding success" of the novel lay in Wyndham's "creation of humanly understandable characters that are, after all, something more and less than human" and concluded that the novel "will be well noted and long remembered".
The critic and science fiction author Damon Knight wrote that Wyndham "failed to realize how good a thing he had. The sixth toe was immensely believable, and sufficient; but Wyndham has dragged in a telepathic mutation on top of it; has made David himself one of the nine child telepaths, and hauled the whole plot away from his carefully built background, into just one more damned chase with a rousing cliche at the end of it ... this error is fatal."
SFreviews.net gave a mixed review, stating that "The Chrysalids comes heart-wrenchingly close to being John Wyndham's most powerful and profound work", but that "Wyndham stumbles—catastrophically—at the climax, in a way that actually undermines the story's thematic foundations".
The novel also got some positive reviews. The Ottawa Citizen judged the novel as "brilliant" and "a top-notch piece of sci-fi that should be enjoyed for generations yet to come". The Guardian described it as "a remarkably tender story of a post-nuclear childhood" and "a classic to most of its three generations of readers". Hartford Courant reviewer George W. Earley praised it as "a compelling story and Mr. Wyndham's best novel to date."
Galaxy reviewer Groff Conklin praised the novel as "so skillfully done that the fact that it's not a shiny new idea makes absolutely no difference". Anthony Boucher similarly found the novel made "something completely fresh" out of a familiar theme, commending Wyndham's "accumulation of minutely plausible detail" and "greater depth and maturity than he has shown in previous novels". Writing in Astounding, P. Schuyler Miller reported that Wyndham "has made the Mutant theme believable in a way that Odd John, Slan and the stories of the Baldies never quite were".
There is critical disagreement regarding whether the intervention of the Sealand culture at the end of the novel should be considered a deus ex machina.
Critics have disagreed with Wyndham's implication that two differently evolved species must necessarily fight to the death. Wyndham justifies this in a lengthy speech from the Sealand woman near the end of the novel, but her reasoning seems at odds with the implicit plea for tolerance in the earlier part of the novel. This implication also exists in The Kraken Wakes and The Midwich Cuckoos.