In this paper, a novel sliding mode control scheme is developed for continuous stirred tank reactors (CSTRs) in the simultaneous presence of the non-minimum phase behavior and process uncertainties. To circumvent the negative effect of the inverse response in the control scheme a statically equivalent output map (SEOM) is incorporated. Based on a zero-placement method, an effective algorithm for synthesizing the SEOM is presented. Through the help of the SEOM, a gain-adaptive sliding mode controller is constructed to provide stable and robust closed-loop performance. In addition, the potential use of a sliding observer along with the proposed scheme is investigated in this work. Extensive simulation results reveal that the proposed design methodology is applicable and promising for the regulation of CSTRs in the presence of the non-minimum phase and process uncertainties.