Self-compacting concrete (SCC) is a special type of concrete that is highly flowable, nonsegregating and spread into place by its own weight, completely filling the formwork even in the presence of dense reinforcement and then encapsulating the rebar without the need for any additional compaction. This research was carried out to evaluate the effects of bentonite clay and wheat straw ash as a partial substitution for cement in SSC. Bentonite clay and wheat straw ash were added in proportion of 0%, 5.0%, 10%, 15%, and 20% of the weight of the cement. Fresh characteristics were evaluated based on its passing ability and flowability using slump flow, slump T50, L-box, and V-funnel tests. After 7 days, 14 days, and 28 days of curing, cylinders of standard size were cast and tested for compressive and split tensile strength. The test results indicate that bentonite clay and wheat straw ash decrease the passing ability and filling ability of SCC. Furthermore, the concrete specimens’ tests indicate that wheat straw ash and bentonite clay additions of up to 10% and 15% of the weight of the cement tend to improve the compressive and split tensile strength of hardened SCC. Response surface methodology (statistical models) is used to optimize the combined dosage of wheat straw ash and bentonite clay and is verified through experimental tests. It can also be suggested that bentonite and wheat straw ash are successfully neutralized in concrete instead of cement.