The effect of compressibility on the single-mode Rayleigh–Taylor instability is examined using two (2D) and three-dimensional (3D) direct numerical simulations. To isolate compressibility from background stratification effects, this work employs a constant density profile on each side of the interface. The numerical simulations are performed at various Reynolds numbers using the gas kinetic method for static Mach numbers up to M = 0.4. The most important finding is that compressibility acting in isolation enhances the instability and perturbations grows faster with increasing Mach number, unlike previous results with background isothermal state, which show suppression of the instability at higher static Mach numbers. In addition, compressibility is also shown to increase the bubble-spike asymmetry. While the instability grows faster for the 3D case, the findings are qualitatively similar in 2D and 3D. The dynamical reasons underlying the effect of compressibility are elucidated by examining the evolution of vorticity and turbulent kinetic energy transport equations.