The first description of what may have been Coxiella burnetii was published in 1930 by Hideyo Noguchi, but since his samples did not survive, it remains unclear as to whether it was the same organism.

The definitive descriptions were published in the late 1930s as part of research into the cause of Q fever, by Edward Holbrook Derrick and Macfarlane Burnet in Australia, and Herald Rea Cox and Gordon Davis at the Rocky Mountain Laboratory (RML) in the United States.

[4] Research in the 1960s–1970s by French Canadian-American microbiologist and virologist Paul Fiset was instrumental in the development of the first successful Q fever vaccine.

C. burnetii exploits the αVβ3 integrin to enter using RAC1-dependent phagocytosis, which is believed to have evolved as a mechanism to avoid the induction of an inflammatory response.

In the first six hours post-infection, endosomes, autophagosomes, and lysosomes containing acid phosphatase fuse with the nascent phagosome to form early PV, which fosters the transition from SCV to LCV.

[citation needed] The bacteria use a type IVB secretion system known as Icm/Dot (intracellular multiplication / defect in organelle trafficking genes) to inject over 100 effector proteins into the host.

[12][13][14] In Legionella pneumophila, which uses the same secretion system and also injects effectors, survival is enhanced because these proteins interfere with fusion of the bacteria-containing vacuole with the host's degradation endosomes.

[16] At least 75[17] completely sequenced genomes of Coxiella burnetii strains exist,[18] which contain about 2.1 Mbp of DNA each and encode around 2,100 open reading frames; 746 (or about 35%) of these genes have no known function.

QpH1 carries virluence factors important for the bacterium's survival inside mouse macrophages[20] and Vero cells; growth on axenic media is unaffected.