Although reference ranges of perinatal behavior of mule foals are paramount for intervention of compromised animals, there are no published data. The objective of this study was to compare the behavior and perinatal physiologic characteristics of mule and equine foals and the time for fetal membrane expulsion. A total of 47 healthy foals were evaluated (n = 30 mule and 17 equine foals). Apgar score at birth, 5, 10, 30, and 60 min postpartum, time to sternal recumbency, start suckling reflex, stand, onset of suckling, meconium elimination, and time to fetal membrane expulsion were recorded. A model using Apgar with group, time, and interaction using time as repeated measures and a Tukey test were performed with significance P ≤ 0.05. Mule foals had higher Apgar than equine foals (7.93 ± 0.02 and 7.60 ± 0.07, respectively; P < 0.001). Additionally, mule foals started suckling faster (49.3 ± 2.71 min) than equine foals (81.86 ± 8.41 min; P < 0.001); however, meconium was eliminated slower in mule than equine foals (255.83 ± 18.14 and 76.66 ± 7.79 min, respectively; P < 0.001). Fetal membrane elimination was faster in mares pregnant with mule foals than those pregnant with domesticated horse foals (35.00 ± 4.06 and 113.38 ± 24.70 min, respectively; P = 0.0004). Therefore, mules have different perinatal behavior than equine foals which results in faster adaptation to the extrauterine environment.