Polygamy in this research is defined as a marital relationship where a man marries more than one wife; though there are other two forms of polygamy. In ancient human societies, polygamy had been practiced almost all over the world. But these days, it is most prevalently practiced in Africa than any other area; especially the West African countries practice it more than the other African countries. Despite the prohibition and discouragement of this practice by national and international frameworks, it is being practiced still in many places including Ethiopia. The primary objective of this research was hence to explore the practice of polygamy, and challenges and opportunities of second wife women in polygamous marriages in Mekane Eyesus Town, South Gondar Zone. To this end, a qualitative research approach with case study design was implemented to do this research at Mekane Eyesus Town from February – May 2021 GC. Three key informant interviews, ten in-depth interviews and two FGDs were conducted to collect data for this research. So, there were totally 30 partciapnts (3 key informants, 10 indepth interviewees and 17 FGD discussants). Purposive sampling method was used for FGDs and KIIs whereas snowball sampling was used for selecting second wife women (Qimit). All data were audio recorded and the records were then transcribed and translated to English. Thematic content analysis method was employed to analyze the data. So, it was found that polygamy is still being practiced in Mekane Eyesus town. The common form of polygamy in the area is non-sororal, secret type and the one where the co-wives reside in their separate and distant dwellings. It was also explored that there are many challenges that the second wife women face because of such relationship and those challenges were summarized into 27 codes and four main themes; economic, social, psychological & health related challenges, and challenges related to personal freedom and security. Similarly there are some opportunities that the second wife women get though the challenges overweigh the opportunities. The opportunities found in this research were coded into 14 final codes and four main themes in similar way as challenges. Those are economic, social, psychological & health related opportunities, and personal freedom & protection related opportunities. In general, there are many challenges and few opportunities that the second wife women get in this study area and most of the findings are inline with many other studies. Yet there are many challenges and few opportunities which are distinct to our study area. It can therefore be concluded that second wife women have encountered many challenges but enjoyed few opportunities and this senario would make them to lead spiteful matrimonial life. Hence, the community shall discuorgae this harmful practice, and the town administration and stakeholders shall also design startegies towards prohibiting this practice through creating job opportunities for women in economic difficulties. The women shall also avoid such type of relationship as the challenges overweigh much more than the opportunities.