Mach number and initial conditions effects on Richtmyer–Meshkov (RM) mixing are studied by the vertical shock tube (VST) at Los Alamos National Laboratory (LANL). At the VST, a perturbed stable light-to-heavy (air–SF6, A = 0.64) interface is impulsively accelerated with a shock wave to induce RM mixing. We investigate changes to both large and small scales of mixing caused by changing the incident Mach number (Ma = 1.3 and 1.45) and the three-dimensional (3D) perturbations on the interface. Simultaneous density (quantitative planar laser-induced fluorescence (PLIF)) and velocity (particle image velocimetry (PIV)) measurements are used to characterize preshock initial conditions and the dynamic shocked interface. Initial conditions and fluid properties are characterized before shock. Using two types of dynamic measurements, time series (N = 5 realizations at ten locations) and statistics (N = 100 realizations at a single location) of the density and velocity fields, we calculate several mixing quantities. Mix width, density-specific volume correlations, density–vorticity correlations, vorticity, enstrophy, strain, and instantaneous dissipation rate are examined at one downstream location. Results indicate that large-scale mixing, such as the mix width, is strongly dependent on Mach number, whereas small scales are strongly influenced by initial conditions. The enstrophy and strain show focused mixing activity in the spike regions.