Aim: Microbiology, sensory and shelf life evaluation of wheat-cassava bread from raw materials to finished products. Study Design: Completely randomized design with two replications and average values calculated for mean comparison. Place and Duration of Study: Food/Industrial Laboratory, Department of Microbiology, University of Port Harcourt, Nigeria and Department of Medical Laboratory Science, Niger Delta University, Nigeria, from June 2018 to March, 2019. Methodology: Microbiological, proximate, physicochemical, sensory and shelf-life characteristics of wheat-cassava bread produced using different formulations (90:10; 80:20; 70:30; 60:40) and control 100% wheat-bread were investigated during storage at 32±2°C, using standard methods. Bread were baked at 180°C and 200°C. Two independent determinations were analyzed using ANOVA and significance of the mean differences determined at P=.05. Results: Mean total heterotrophic counts (THC) of raw flour samples increased from 5.41 to 7.62 log10 cfu g-1; total coliform from, 1.08 to 1.90 log10 cfu g-1; and total fungal counts from 2.46 to 4.88 log10 cfu g-1 with increasing cassava flour substitution. Mean values for THC and total fungal counts of baked bread samples increased from 1.88 to 7.73 log10 cfu g-1 and 0.48 to 4.05 log10 cfu g-1 respectively from day 0 to day 6. However, coliforms were not detected in baked bread. The predominantly isolated bacteria were: Bacillus, Aerococcus and Staphylococcus while fungi were: Aspergillus, Penicillium and Fusarium. Proximate composition showed that carbohydrate and ash contents increased from 46.07 to 55.29% and 1.35 to 3.79% respectively while crude protein and moisture contents decreased from 14.01 to 8.08% and 29.0 to 23.8% respectively and pH from 6.59 to 6.14 with increasing cassava flour substitution. Conclusion: The overall acceptability of the wheat/cassava bread reduced with increasing cassava flour concentration, however, there was no significant difference (P=.05) in the overall acceptability of the 100% wheat bread and that of 90:10% till day four.