The Isthmus of Panama comprises a lithologically diverse andesitic oceanic arc of Late Cretaceous to Holocene age; it has large spatial variation in rainfall, displays a large range of physical erosion rates, and, therefore, is an ideal location to examine silicate weathering in the tropics. We use a multiyear data set of river chemistry for a 450 km transect across the Cordillera Central of west-central Panama to investigate controls on chemical weathering in tropical small mountainous rivers. Sea-salt corrected cation weathering yields (Casil + Mgsil + Na + K) range over more than an order in magnitude from 3.1 to 31.7 t/km2/yr, while silicate weathering yields (Casil + Mgsil + Na + K + Si) range from 6.9 to 69.5 t/km2/yr. Watershed lithology is the primary control on riverine chemistry, but landscape topographic character and land cover and/or land use also influence solute delivery potential. Strong statistical links of small mountainous river chemical weathering fluxes with rainfall and physical weathering rates attest to the importance of runoff and erosion in maintaining elevated bedrock weathering rates. CO2 consumption ranges from 155 × 103 mol/km2/yr to 1566 × 103 mol/km2/yr, in the upper range of global rates, leading us to suggest that andesite terrains should be considered separately when calculating removal of CO2 from the atmosphere via silicate weathering.