A cross-sectional study was conducted to determine prevalence and risk factors of ruminal disorders with identification of pathophysiological changes of rumen fluid and blood in sheep from January to June, 2019 in and around Gondar town, Northwest Ethiopia. One hundred seventy two sheep were selected by systematic random sampling technique and 21 apparently healthy sheep were selected by purposive sampling technique. Complete case history and clinical signs were recorded. Samples (rumen fluid and blood) were collected and analysed in the laboratory. The data was analysed using SPSS version 20. The prevalence of ruminal disorders in sheep was 55.2% and identified major types of ruminal disorders were simple indigestion (25.6%), ruminal acidosis (20.35%), ruminal tympany (5%) and ruminal alkalosis (4.1%). The most prominent clinical signs recorded in sheep with ruminal disorders were anorexia and inappetence followed by diarrhoea, dullness, dehydration, bloat and abdominal pain. Ruminal motility and protozoal motility were significantly (p<0.05) reduced where as percentage of PCV was significantly increased (p<0.05) in sheep's with ruminal disorders.Sedimentation activity time was significantly reduced in sheep with ruminal acidosis however, it was significantly (p<0.05) increased in ruminal alkalosis (p<0.05). Color, consistency and odour were affected during ruminal disorders. In multivariable logistic regression analysis showed that Male sex; (Adjusted Odds Ratio [AOR] = 6.044; 95% CI: 1.894-19.281), extensive farming system (AOR=6.358; 95% CI: 1.335-30.285), Crop residue and concentrate feed (AOR=23.01; 95% CI: 8.364-08.201), sudden change of feed (AOR=32.911, 95% CI: 7.959-136.092) and moldy feed (AOR=20.807, 95%CI: 6.245-69.325) were significantly (p<0.05) associated with occurrence of ruminal disorders in sheep.