ABSTRACT Active Galactic Nuclei (AGN) are believed to provide the energy that prevents runaway cooling of gas in the cores of galaxy clusters. However, how this energy is transported and thermalized throughout the Intracluster Medium (ICM) remains unclear. In recent work, we showed that streaming cosmic rays (CRs) destabilize sound waves in dilute ICM plasmas. Here, we show that CR streaming in the presence of gravity also destabilizes a pressure-balanced wave. We term this new instability the CR buoyancy instability (CRBI). In stark contrast to standard results without CRs, the pressure-balanced mode is highly compressible at short wavelengths due to CR streaming. Maximal growth rates are of order (pc/pg)β1/2ωff, where pc/pg is the ratio of CR pressure to thermal gas pressure, β is the ratio of thermal to magnetic pressure, and ωff is the free-fall frequency. The CRBI operates alongside buoyancy instabilities driven by background heat fluxes, i.e. the heat-flux-driven buoyancy instability (HBI) and the magneto-thermal instability (MTI). When the thermal mean free path lmfp is ≪ the gas scale height H, the HBI/MTI set the growth rate on large scales, while the CRBI sets the growth rate on small scales. Conversely, when lmfp ∼ H and (pc/pg)β1/2 ≳ 1, CRBI growth rates exceed HBI/MTI growth rates even on large scales. Our results suggest that CR-driven instabilities may be partially responsible for the sound waves/weak shocks and turbulence observed in galaxy clusters. CR-driven instabilities generated near radio bubbles may also play an important role redistributing AGN energy throughout clusters.