This study was carried out to determine the chemical composition and in situ degradability of agro-industrial by-products found in Eritrea. Three categories of by-products were evaluated and were the milling industry (wheat bran; WB, short; WS, and middling; WM), brewery (brewers’ dry grain; BDG, hops; BDH, and yeast; BDY) and sesame cakes (sesame cake machine extracted; SCM and manually extracted; SCT). The dry matter (DM) varied between 88.46% in BDY to 92.39% in SCT. The lowest (P < 0.05) crude protein (CP) content was recorded in WM at 10.11% while the highest was from the BDY at 48.20%. The metabolisable energy (ME) value of the agro-industrial by-products ranged from 8.72 to 11.18 MJ per kg DM with the BDH recording the lowest value (P < 0.05). The sesame cakes (SCM and SCT) recorded higher values of 11.17 and 11.18 MJ per kg DM respectively. The SCT recorded the highest ash content at 10.93% followed by BDY at 10.16% with the least being obtained from WM at 2.48%. The ether extract and acid detergent lignin contents were generally low in all cases for all the by-products. Generally, the results indicated that there was no clear pattern in terms of nutrients content amongst the by-products. The in situ DM, organic matter (OM) and CP degradability differed amongst and within the sesame cakes, milling and brewery by-products. The wide variation in chemical composition, DM, OM, CP degradability, and ME obtained from this study offer farmers huge flexibility in formulating rations according to the productive performance of target animals.