Simple Summary: Most post-harvest interventions for addressing Salmonella in beef products are applied directly to the carcass surface and are ineffective at reducing or eliminating Salmonella that are harbored in cattle lymph nodes. Bacteriophages are viruses that are ubiquitous in the environment, including agricultural facilities, that only infect and destroy bacterial cells. The objectives of this experiment were to determine whether natural bacteriophage populations contained in manure slurry or laboratory-curated bacteriophage cocktails could reduce Salmonella prevalence on feedlot pen surfaces and on cattle hides and subsequently in cattle lymph nodes. Applications of manure slurry and bacteriophage cocktail treatments reduced the prevalence of Salmonella on cattle hides which may contribute to lymph node contamination. Lymph nodes may become incorporated into ground beef products, which can contribute to beef-related foodborne illness, and therefore, these treatments have the potential to address food safety concerns. Post-harvest Salmonella mitigation techniques are insufficient at addressing Salmonella harbored in cattle lymph nodes, necessitating the exploration of pre-harvest alternatives that reduce Salmonella prior to dissemination to the lymph nodes. A 2 × 2, unbalanced experiment was conducted to determine the effectiveness of pre-harvest treatments applied to the pen surface for Salmonella mitigation in cattle. Treatments included manure slurry intended to mimic pen run-off water (n = 4 pens), a bacteriophage cocktail (n = 4), a combination of both treatments (n = 5), and a control group (n = 5) that received no treatment. Environment samples from 18 feedlot pens and fecal grabs, hide swabs, and subiliac lymph nodes from 178 cattle were collected and selectively enriched for Salmonella, and Salmonella isolates were sequenced. The combination treatment was most effective at reducing Salmonella, and the prevalence was significantly lower compared with the control group for rump swabs on Days 14 and 21. The treatment impact on Salmonella in the lymph nodes could not be determined due to low prevalence. The reduction on cattle hides suggests that bacteriophage or water treatments applied to the feedlot pen surface may reduce Salmonella populations in cattle during the pre-harvest period, resulting in reduced contamination during slaughter and processing. [ABSTRACT FROM AUTHOR]