Salmonella spp. infections are considered as the most common food-borne disease globally. The contamination of food products with Salmonella has given rise to severe health and economic challenges. This study assessed the prevalence of Salmonella in the faeces of cows and goats in the Eastern Cape province of South Africa, their antibiotic resistance patterns as well as antibiotic-resistant gene determinant. Antibiotic disc was used for antibiogram profiles while polymerase chain reaction was employed for the detection of antibiotic-resistant genes. A total of 150 Salmonella were isolated from the faecal samples. Eighty two (55%) isolates were recovered from cow faeces while 68 (45%) were isolated from goat faeces. All Salmonella isolates were sensitive to ciprofloxacin (100%) while 95% were sensitive to ofloxacin. Also, a high sensitivity of 93 and 89% was observed against nalidixic acid and ofloxacin, respectively. Salmonella isolates demonstrated moderate sensitivity against cephalothin (70%), chloramphenicol (75%) and minocycline (68%) while 49% were resistant to tetracycline and erythromycin. The prevalence of the antibiotic-resistant genes in Salmonella isolates were detected as follows: integron conserved segment 28% (42/150), bla TEM gene 19.3% (29/150), blapse₁ 7.3% (11/150) and blaampC 4.7% (7/150). The results obtained in the study imply that cow and goat faeces could be potential reservoirs of Salmonella and could possibly cause infections as a result of contamination of food products. There is a need for a surveillance system to track resistance patterns of Salmonella circulating in South Africa.