Transmission occurs when raw or undercooked freshwater crabs or crayfish containing larvae (metacercariae) are ingested. The metacercariae excyst in the small intestine and penetrate the abdominal cavity, where they remain for a few days before migrating to the lungs. P westermani and P heterotremus mature within the lungs over 6 to 10 weeks, when they then begin egg production. Eggs escape from pulmonary capsules into the bronchi and exit from the human host in sputum or feces. Eggs hatch in freshwater within 3 weeks, giving rise to miracidia. Miracidia penetrate freshwater snails and emerge several weeks later as cercariae, which encyst within the muscles and viscera of freshwater crustaceans before maturing into infective metacercariae. Transmission also occurs when humans ingest raw pork, usually from wild pigs, containing the juvenile stages of Paragonimus species (described as occurring in Japan).

Humans are accidental ("dead-end") hosts for P skrjabini and P miyazakii . These flukes cannot mature in humans and, hence, do not produce eggs.

Paragonimus species also infect a variety of other mammals, such as canids, mustelids, felids, and rodents, which can serve as animal reservoir hosts.

The incubation period is variable; egg production begins approximately 8 weeks after ingestion of P westermani metacercariae.