The Galápagos Spreading Center (GSC) between 90.5°W and 98°W manifests its interaction with the nearby Galápagos plume by way of variations in lava geochemistry, crustal thickness, and morphology along the ridge axis. Natural glasses from stations with ∼9 km average spacing were analyzed for major and minor elements, H2O, and CO2. Samples can be classified as enriched mid‐ocean ridge basalts (E‐MORB), transitional MORB (T‐MORB), or normal MORB (N‐MORB) on the basis of K/Ti ratios. E‐MORB dominate the GSC east of 92.6°W. T‐MORB are mainly found between 92.6°W and 95.5°W. West of the propagating rift tip at 95.5°W, N‐MORB dominate. High K/Ti E‐MORB also have higher H2O, Al2O3, and Na2O and lower FeO*, SiO2, and CaO/Al2O3 relative to N‐MORB at similar values of MgO, characteristics consistent with lower mean extents of partial melting relative to N‐MORB. We examine the melting process along this section of the GSC with a set of equations that simulate a deep zone of hydrous melting related to the depression of the mantle solidus by H2O. This model constrains the range of mantle source compositions, the depth of the additional hydrous melting zone, the melt productivity in the hydrous region, and the ratio of mantle flow rate through the hydrous zone relative to the anhydrous zone (Uw/U0) that can explain the measured crustal thickness as well as the fractionation‐corrected concentrations of K, Na2O, H2O, and Ti along the GSC. Far from the hot spot, the measured crustal thickness and N‐MORB compositions are explained by passive mantle upwelling (Uw/U0 = 1), mean melt fraction () ∼ 0.06, and a source with ∼35 ppm K, 130 ppm H2O, 2300 ppm Na2O, and 1050 ppm Ti. The transitional zone has a source enriched in K and could have a slight excess plume‐driven flow through the hydrous melting zone (Uw/U0 ≤ 1.5). The crustal thickness and glass compositions in the “enriched” region of the GSC nearest the hot spot are best explained by only a slight increase in the temperature of the mantle (<∼20°C), coupled with a mantle source moderately enriched (relative to N‐MORB source) and plume‐driven flow through the hydrous zone of Uw/U0 = 1.5–3.5.