Endocrine-disrupting chemicals found in many commercial products may interfere with the normal functioning of the endocrine system and are unsafe because of their cumulative effect on the human body. However, little is known about the effects of combinations of endocrine-disrupting chemicals in humans. Methoxychlor and bisphenol A are toxic to male reproductive organs. Therefore, we studied the effects of methoxychlor and bisphenol A on male reproductive function. Male mice were divided into four treatment groups: control, 400 mg methoxychlor, 1 mg bisphenol A, and 400 mg methoxychlor + 1 mg bisphenol A/kg/day. Methoxychlor and bisphenol A were dissolved in sesame oil and acetone and administered orally for 4 weeks. After administration, the weight and histological changes in the testicles and epididymis, sperm count and health were observed biochemical tests and whole blood counts were performed. The results showed that the mice in the bisphenol A and methoxychlor + bisphenol A groups gained more weight than those in the control and methoxychlor group. The weights of the testes and epididymis were higher in the experimental groups than in the control. Sperm motility and progression were significantly reduced in the bisphenol A and methoxychlor + bisphenol A groups. Histological observation showed a reduced number of sperm, smaller seminiferous tubules, and destroyed lumen in the methoxychlor + bisphenol A group compared to the other groups. In conclusion, our study showed that methoxychlor and bisphenol A destroy male reproductive tissues and decrease sperm quality.