Abstract Iridate oxides display exotic physical properties that arise from the interplay between a large spin–orbit coupling and electron correlations. Here, we present a comprehensive study of the effects of hydrostatic pressure on the electronic transport properties of SrIrO₃ (SIO), a system that has recently attracted a lot of attention as potential correlated Dirac semimetal. Our investigations on untwinned thin films of SIO reveal that the electrical resistivity of this material is intrinsically anisotropic and controlled by the orthorhombic distortion of the perovskite unit cell. These effects provide another evidence for the strong coupling between the electronic and lattice degrees of freedom in this class of compounds. Upon increasing pressure, a systematic increase of the transport anisotropies is observed. The anomalous pressure-induced changes of the resistivity cannot be accounted for by the pressure dependence of the density of the electron charge carriers, as inferred from Hall effect measurements. Moreover, pressure-induced rotations of the IrO₆ octahedra likely occur within the distorted perovskite unit cell and affect electron mobility of this system.