Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin, or alternatively, when the body cannot effectively use the insulin it produces and characterized by hyperglycemia, due to lack of insulin secretion, insulin action or both. Type 2 diabetes mellitus (T2DM) remains a public health problem in the world. The main purpose of this study was to find out a possible association between human ABO-Rhesus (RH) blood groups and socio demographic factors with T2DM in Awi Zone, North West Ethiopia. A retrospective hospital based study was conducted to collect representative samples with a stratified random sampling technique. Data on socio-demographic factors such as age, sex, residence and clinical data such as ABO blood group (A, B, AB,O), Rh factors (Rh positive and Rh negative) and blood glucose level (glycemic level) were collected from a total of 403 individuals, 202 diabetic patients and 201 non-diabetic healthy controls from confirmed T2DM medical records (patients examination and laboratory registration book) and healthy controls medical records (examination and laboratory registration book). The data was entered in Excel and analyzed using SPSS version 26. Most 77(38.2%) T2DM cases occurred between the age category of 51 60 with mean age of 57.34 ( 12.40) and minimum and the maximum of 35 and 86 years old respectively. Age and blood group showed statistically significant associated with T2DM but sex, resident and Rh factor had no statistically significant associated with T2DM in multivariate regression analysis. Blood group O 136(33.7%) was the most frequently occurred blood type from the overall distribution of the sampled populations while blood type A 80(39.6%) and O 91 (45.3%) are the predominant blood types in T2DM cases and healthy controls respectively. The multivariable analysis showed that age group of 51-60 and above 60 years old were 370.66 times (AOR=370.66: 95% CI: 78.28,1755.19) and 176.23 times (AOR=176.23; 95% CI: 38.60,804.59) more likely to be T2DM than individuals in the age range of below 30 years old respectively. The odds of developing T2DM in individuals having blood group O were 0.34 times (AOR=0.34; 95% CI: 0.17, 0.69) lower than blood group A. This study suggested that human beings having blood group A had a higher risk of developing T2DM, but blood type AB had a lower risk of T2DM. Key words: Association, Socio-demographic factors, ABO blood groups, Rhesus factor, glycemic level and Type 2 diabetes mellitus.