A Small proportion of brewer’s spent yeast (BSY) is used as a protein source to replace costly but conventionally used agro-industrial by-product feeds in Ethiopia with large volumes seen accumulated at production sites causing disposal and public health problems. Consequently, there is a need to develop appropriate ways of using this by-product as livestock feed. This study was conducted to evaluate the effect BSY inclusion level and ensiling duration (ED) on fermentative, fungal load dynamics, and nutritional characteristics of fresh brewer’s spent-yeast based silage. Fresh brewery by-product samples were obtained from Heineken beer factory whereas wheat bran (WB) used as an input for formulating the silage material was purchased from a nearby animal feed processing plant. The ratio of brewery spent grain (BSG) to WB used majorly as protein and energy sources, respectively were 30:69 with 1% salt addition. To prepare the silages materials, 4 BSY inclusion levels (0, 10, 20 and, 30%) to replace BSG and 3 ED (2,4 and 6 weeks) were arranged in 4x3 factorial combination using completely randomized design (CRD) in 5 replications. Parameters measured include: observation for surface spoilage, yeast and mold colony count, silage temperature, pH, total dry matter loss (TDML), major proximate, detergent fractions and permanganate lignin, in-vitro organic matter digestibility (IVOMD) and estimated metabolizable energy (EME) values. The study revealed that at any BSY inclusion level and ED, extensive mold growths and discolorations were not observed. However, slightly higher values of 6.5, 5.7, and 12.2 colony forming unit (CFU)/g DM yeast, mold and total fungal counts (TFC), respectively were recorded only at the 6 weeks of the fermentation period with 30% BSY inclusion level. Brewer’s spent yeast inclusion level and ED had significant (P < 0.05) effect on silage temperature (mean = 18.05 0C) and pH (mean = 4.16). Among proximate and detergent values, crude protein (mean CP g/kg DM = 204.5), neutral detergent fiber (mean NDF g/kg DM = 552.9), and acid detergent fiber (mean ADF g/kg DM = 115.9) responded significantly (P < 0.05) to both BSY inclusion levels and ED. Among nutritional quality, CP, IVOMD, and EME of silage samples were subjected to substantial improvements when silage masses were prepared from 20% BSY inclusion levels and when the same silage materials were allowed to ferment for four weeks. Therefore, before making any further recommendation it is, thus, important to verify the current finding with additional animal response trials that take both biological and economic feasibilities into account.