The impacts of different replacement levels of micro silica (MS), fly ash (FA), and the combined usage of MS and FA on the behavior of concrete were investigated. Design of experts has been used incorporating the response surface methodology to find the synergetic effect of FA and MS on fresh and hardened concrete properties. A total of 15 and 30% of the binder content were replaced by FA. As well as a total of 5 and 10% of the binder content were replaced by MS. Experimental results of concrete mixtures have been used to construct ANOVA models. These models have also been confirmed to expect the properties of concrete mixtures based on different fractions of FA ash and MS. All statistical models are significant because P-value is less than 5%, and the difference between predicted R ² and adjusted R ² is lower than 20%. The variation between confirmation tests for the optimized mixture and test results are lower than 5%.