Amanita exitialis is a lethal mushroom found in China. Knowledge regarding taxonomic characterization, toxin detection, general poisoning conditions, clinical manifestations, laboratory examinations, and clinical treatments for this species is currently lacking. We investigated three A. exitialis mushroom poisoning cohorts in Yunnan Province in 2014 and 2015, involving 10 patients. Mushroom samples were identified by morphological and molecular studies. Ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry was used to detect the peptide toxins in the mushroom samples. Epidemiological information, clinical data, and results of laboratory examinations were collected and analyzed. The mushroom samples were all identified as A. exitialis. The average toxin concentration decreased from the cap to the stipe to the volva, and the average concentration of the peptide toxins decreased in the order of α-amanitin > phallacidin > β-amanitin > γ-amanitin. The latency period between ingestion and the onset of symptoms was 13.9 ± 2.1 h, and the time from ingestion to hospitalization was 49.6 ± 8.5 h. The most common symptoms were nausea and vomiting (100%). Four patients died from fulminant hepatic failure. Laboratory examinations showed that the alanine transaminase, aspartate transaminase, prothrombin time, and activated partial thromboplastin time levels peaked on the third day post-ingestion. Total bilirubin and direct bilirubin values peaked on day 7. The death group and the survival group had a similar variation trend of serological indexes, but the death group had a greater change. A. exitialis is an extremely dangerous mushroom and there is a need to educate the public to avoid picking and eating wild mushrooms that have not been definitively identified.