Chemical analyses from 71 watersheds across an ∼450 km transect in west-central Panama provide insight into controls on weathering and rates of chemical denudation and CO2 consumption across an igneous arc terrain in the tropics. Stream and river compositions across this region of Panama are generally dilute, having a total dissolved solute value = 118 ± 91 mg/L, with bicarbonate and silica being the predominant dissolved species. Solute, stable isotope, and radiogenic isotope compositions are consistent with dissolution of igneous rocks present in Panama by meteoric precipitation, with geochemical signatures of rivers largely acquired in their upstream regions. Comparison of a headwater basin with its entire watershed observed considerably more runoff production from the high-elevation upstream portion of the catchment than in its much more spatially extensive downstream region. Rock alteration profiles document that weathering proceeds primarily by dissolution of feldspar and pyroxene, with base cations effectively leached in the following sequence: Na > Ca > Mg > K. Control on water chemistry by bedrock lithology is indicated through a linking of elevated ([Na + K]/[Ca + Mg]) ratios in waters to a high proportion of catchment area silicic bedrock and low ratios to mafic bedrock. Sr-isotope ratios are dominated by basement-derived Sr, with only very minor, if any, contribution from other sources. Cation weathering of Casil + Mgsil + Na + K spans about an order in magnitude, from 3 to 32 tons/km2/yr. Strong positive correlations of chemical denudation and CO2 consumption are observed with precipitation, mean watershed elevation, extent of land surface forest cover, and physical erosion rate.