We find evidence for the impact of infalling, low-metallicity gas on the Galactic disk. This is based on FUV absorption line spectra, 21 cm emission line spectra, and far-infrared (FIR) mapping to estimate the abundance and physical properties of IV21 (IVC135+54-45), a galactic intermediate-velocity molecular cloud that lies ∼300 pc above the disk. The metallicity of IV21 was estimated using observations toward the subdwarf B star PG1144+615, located at a projected distance of 16 pc from the cloud's densest core, by measuring ion and H i column densities for comparison with known solar abundances. Despite the cloud's bright FIR emission and large column densities of molecular gas as traced by CO, we find that it has a sub-solar metallicity of log(Z/Z ) = −0.43 ± 0.12 dex. IV21 is thus the first known sub-solar metallicity cloud in the solar neighborhood. In contrast, most intermediate-velocity clouds (IVC) have near-solar metallicities and are believed to originate in the Galactic Fountain. The cloud's low metallicity is also atypical for Galactic molecular clouds, especially in light of the bright FIR emission which suggest a substantial dust content. The measured I 100 μm /N (H i) ratio is a factor of three below the average found in high latitude H i clouds within the solar neighborhood. We argue that IV21 represents the impact of an infalling, low-metallicity high-velocity cloud that is mixing with disk gas in the lower Galactic halo.