Structure-switching sensors utilize recognition elements that undergo a conformation change upon target binding that is converted into a quantitative signal. Electrochemical, aptamer-based sensors achieve detection of analytes through a conformation change in an electrode-bound, oligonucleotide aptamer by measuring changes in electron transfer efficiencies. The analytical performance of these sensors is related to the magnitude of the conformation change of the aptamer. The goal of the present work is to develop a general method to predictably tune the analytical performance (sensitivity and linear range) of electrochemical, aptamer-based sensors by utilizing a mixture of rationally designed aptamer sequences that are specific for the same target but with different affinities on the same electrode surface. To demonstrate control over sensor performance, we developed heterogeneous sensors for two representative small molecule targets (adenosine triphosphate and tobramycin). We demonstrate that mixtures of modified sequences can be used to tune the affinity, dynamic range, and sensitivity of the resulting sensors predicted by a bi-Langmuir-type isotherm.