Background During January 2017-December 2018, multiple human anthrax outbreaks in Arua, Kween, and Kiruhura districts, Uganda were caused by exposure to domestic ruminants that died of anthrax. We investigated to determine the scope of anthrax outbreaks in domestic ruminants, identify possible exposures, and recommend evidence-based control measures. Methods We defined a suspected case-animal as sudden death of a domestic ruminant with unclotted blood oozing from body orifices during January 2016–December 2018 in Arua, Kween and Kiruhura districts. A probable case-animal was a suspected case-animal with a positive rapid diagnostic test using the Active Anthrax Detect Rapid Diagnostic Test, and/or the microscopic identification of Gram-positive rods in biological samples. A case-kraal was defined as an enclosure of cattle/sheep or mixed species with ≥1 suspected case-animal. We reviewed district veterinary records and actively searched for case-livestock. We conducted separate case-control studies in the affected districts to compare exposures between case-kraals and control-kraals (i.e., kraals with no suspected case-livestock during the same time period as the case-kraal), frequency-matched by village, with ratios of 1:1 in Arua, 1:4 in Kiruhura, and 1:2 in Kween. We estimated overall associations in all three districts using pooled analysis. Results We identified 1,971 suspected case-livestock (attack rate [AR] =1.4/1000) in 229 (7.3/1,000) of 31,500 kraals. Cattle (AR=2.1/1,000), goats (AR=0.48/1,000), and sheep (AR=0.10/1,000) were all affected. Of the three districts, Arua was the most affected (AR=3.1/1,000), followed by Kween (AR=1.8/1,000) and Kiruhura (AR=0.065/1,000). The epidemic curve indicated continuous outbreaks in Arua and Kween districts. Human outbreaks were reported during or after the onset of livestock outbreaks in all three districts. Having livestock that died of suspected anthrax butchered <50m from the kraal (OR=8.0; 95%CI=5.2-12) and improper livestock carcass disposal on/near the pastureland (OR=1.7, 95%CI=1.1-2.4) before the outbreak were significant risk factors for being a case-kraal. Conclusions Ugandan districts with human anthrax outbreaks had concurrent livestock anthrax outbreaks associated with nearby butchering and improper carcass disposal of livestock with suspected anthrax. We recommended anthrax vaccination for domestic ruminants, proper carcass disposal, increased surveillance for sudden livestock deaths, increased capacity for laboratory confirmation, and sensitization to livestock-keepers about anthrax control.