Differences exist in reproductive physiology between African buffalo (Syncerus caffer), cattle (Bos taurus) and water buffalo (Bubalus bubalis). The aim of this study was to histo-morphologically compare the anatomy of non-pregnant and pregnant uteri of buffalo and cattle. Two non-pregnant uteri and placentae of six pregnant African buffalo were used. Early placentome formation (fetal crown rump length (CRL): 2–17.5 cm) in S. caffer and B. taurus was compared. The endometrium of buffalo uteri comprises round to ovoid, dome-shaped and gland-free caruncles. A predominantly simple columnar epithelium of non-ciliated cells covers caruncular tissue, while, additionally, ciliated cells occur in the epithelium of the intercaruncular areas and within the simple columnar or pseudostratified epithelium of the endometrial glands. During early gestation, multiple placentomes develop. Unlike the placentomes in cattle at similar CRL, buffalo placentomes do not develop a caruncular stalk. The sessile, dome-shaped buffalo placentome has simple, slightly conical villi branching less than in cattle, thus indicating different and less complex feto-maternal interdigitation than seen in the latter. A synepitheliochorial interhaemal barrier can be expected in the buffalo placenta, as the occurrence and ultrastructure of trophoblast giant cells resemble those described in cattle.