The aim of this study was to identify Salmonella serotypes infecting cattle in Pennsylvania, to compare infection rates for the predominant serotype, Salmonella enterica serotype Cerro, with the infection rates for the same serotype in humans, and to study the clonal diversity and antimicrobial resistance for this serotype in cattle from 2005 to 2010. Clonal diversity among the selected isolates was studied using pulsed-field gel electrophoresis (PFGE) and repetitive (rep)-polymerase chain reaction (PCR). Salmonella Cerro showed the single largest increase as a cause of cattle infections over the study period. The proportional distribution of Salmonella Cerro serotype among laboratory-submitted Salmonella positive cases in cattle was 36.1% in the year 2010 compared to 14.3% in 2005. A simultaneous decrease in serotype Newport infections was also observed in cattle (25% in 2005, to 10.1% in 2010). Studies of clonal diversity for cattle and human isolates revealed a predominant PFGE type but showed some variability. All tested isolates (n = 60) were susceptible to sulfamethoxazole-trimethoprim, but 2% of cattle isolates (n = 1/50) and 20% of human isolates (n = 2/10) showed resistance to tetracycline and sulfisoxazole. One human isolate showed additional resistance to ampicillin and gentamicin. This study suggests an increase in Salmonella Cerro infections in the cattle population and a decrease in Salmonella Newport infections. The increase in Cerro infections appears to be restricted to the cattle population, but occasional human infections occur.