The transient vibroacoustic response mitigation of a rectangular sandwich panel with an adaptive electro-rheological fluid core layer, and backed by a hard-walled reverberant rectangular parallelepiped acoustic enclosure, is investigated. The problem is analyzed in a multidisciplinary framework that involves the thin sandwich electro-rheological fluid-based plate model, the 3D wave equation for the acoustic enclosure domain, the first-order Kelvin–Voigt viscoelastic model for the electro-rheological fluid core material, the pertinent structure–fluid compatibility relation, and the inherently robust sliding mode control strategy. The generalized Fourier expansion method is utilized to set up the fully coupled system equations in the state–space domain, and the fourth-order Runge-Kutta time marching technique is then utilized to compute both uncontrolled and controlled coupled system responses in three basic external loading configurations. It is found that increasing the cavity depth has a substantial restraining effect on the overall sound pressure response levels, while the electro-rheological fluid-panel displacement response amplitudes experience only moderate reductions. Also, a purely passive electro-rheological fluid-based system is observed not to be very effective for vibroacoustic response suppression of the cavity-coupled structural system, while the overall success of the applied sliding mode control methodology in reasonable reduction of both panel displacement and sound pressure time response amplitudes is demonstrated. Furthermore, the control system authority with regard to the acoustic cavity pressure (panel displacement) is found to moderately (slightly) decrease as the cavity depth increases. Limiting cases are considered and accuracy of the suggested analytical model is checked against the output of an FEM package as well as with the accessible literature results. Moreover, the main components of a prospective experimental platform for verifying the performance of proposed vibroacoustic control system are briefly described.