Clostridium perfringens poses a serious threat to small ruminants by causing moderate to severe enterotoxaemia. Due to its ability to produce a wide arsenal of toxins, it is ranked among the most prevalent and important pathogens in livestock. This study focused on the molecular characterization of different Clostridium perfringens types along with their antimicrobial resistance profile. An overall higher prevalence of C. perfringens (46.1%) was detected based on mPCR among sheep and goats (healthy and diseased) in the Punjab province, Pakistan. The majority of the isolates were characterized as type A (82%), followed by type D (18%). Among the isolates from diseased sheep and goats, 27% were positive for cpa, 49% for cpa and cpb2, 9% for cpa and etx, 15% for cpa, cpb2 and etx. In the case of isolates from healthy sheep and goats, 59% were positive for cpa, 34% for cpb2 and cpa, 4% for cpa and etx, and 3% for cpa, cpb2 and etx. The prevalence of the beta2 toxin gene in the diseased sheep and goat population was 64% as compared to 37% in healthy animals. All 184 isolates (100%) were sensitive to rifampin and ceftiofur; the majority (57%) was sensitive to teicoplanin, chloramphenicol, amoxicillin, linezolid and enrofloxacin. A lower proportion of isolates (43%) were sensitive to ciprofloxacin and only 14% were susceptible to erythromycin. The findings of this study highlight the higher prevalence of C. perfringens in small ruminants and indicate that detailed pathogenesis studies are necessary to understand the explicit role of various toxins in causing enteric infections in sheep and goats including how they might be exploited to develop vaccines against these diseases.