Yam farmers in Ghana have, over the years, used herbicides for weed control, particularly glyphosate. Although this has been helpful to them, there are complaints and concerns, among the yam farmers and a section of the public, that the yam tuber rots easily under the use of herbicides. This study, therefore, was set up at the field level to investigate the possibility of herbicides use causing yam rot. Two yam varieties, “laribako” and “olodo”, were grown under the conditions of chemical weed control (use of glyphosate) and manual weed control in three replicate sites in Wulensi in the Nanumba traditional area of northern Ghana. The study revealed that there was no difference in rots between herbicide treated yams and manually weeded yams, but that there was a difference in rots between “laribako” and “olodo” yam varieties. The results also showed that there was no difference in yield between herbicide treated yams and manually weeded yams. Based on the findings, it can be concluded that, there was no difference in yam rot and yield between herbicides treated and manually weeded yams, but “laribako” was more susceptible to rot than “olodo”.