Topographic development of the southern Washington Cascade Range and its influence on regional climate on the leeward side of the range for the past 15.6 m.y. are evaluated, using oxygen isotope ratios (δ18O) of ancient meteoric water recorded in authigenic smectites. The δ18O values of authigenic smectites from paleosols and altered tuffs on the east side of the range exhibit a temporal and continuous decrease of ∼3‰–4‰ from 15.6 Ma to the present. Taking into account a regional temperature change in eastern Washington since the middle Miocene, the calculated δ18O values of regional meteoric water show a negative shift of ∼3.5‰–4.5‰ over the same interval. Such a decrease is similar to the change in the δ18O values of modern precipitation from the coastal side to a region downwind of the Washington Cascades. This negative shift of the calculated δ18O values on the east side of the range is best explained by the development of a rain shadow due to the tectonic rock uplift of the Cascades during the late Cenozoic. Based on the empirically calculated relationship between change in elevation and change in the δ18O value of precipitation, paleorelief of the southern Washington Cascades since 15.6 Ma is estimated to be ∼1.2–1.7 km.