Abstract Liver abscess (LA) prevalence has increased 15% for beef cattle and 25% for Holstein cattle. The prevalence of liver abscesses in the Central Plains region (CR) is greater than the Southwest region (SR) of the United States. The objective was to evaluate soil organic matter (SOM) microbiome of feedlot pens, associated LA microbiomes, and the impact of breed, location, and tylosin. Eighty-three commercial feedlot pens were sampled for SOM prior to harvesting and LA samples were collected from two commercial packing plants in Tolleson, AZ (SR) and Greely, CO (CR). Liver abscess samples were linked to SOM samples. Amplification and sequencing of the V4 variable region of the 16S rRNA gene was performed using the Illumina MiSeq. Bacterial phyla, genera, and diversity indices were reported for LA and SOM samples. Reported data is from a subset of five pens. The most prevalent genera identified in liver abscesses were Fusobacterium (64.2%) and Bacteroides (18.6%). Predominant SOM genera were Atopostipes (13%) and Clostridium (10%). Phylum SOM Shannon Weiner Index (SWI) was lower for the CR compared to the SR (0.034 vs. 0.174; P < 0.05), indicating a dominant bacterium in the CR. Atopostipes and Clostridium comprised 48% of the CR SOM, explaining the lower SWI. The SWI of SOM and liver abscesses of Holsteins are lower (P < 0.05) compared to beef counterparts. Additionally, Clostridium, Fusobacterium, and Atopostipes populations were greater (P < 0.05) in SOM of Holstein pens than beef pens. Genus richness was lower (P < 0.05) for both SOM and liver abscesses from pens of cattle fed tylosin vs. no tylosin. There is a negative correlation between SOM SWI and LA% (R2 = -0.49; P = 0.03) and LA severity (A+) (R2 = -0.44; P = 0.05). In conclusion, SOM may serve as a potential vector for liver abscesses.