There are strong regional trends in the ⁸⁷Sr/⁸⁶Sr ratios and δ¹⁸O values of Miocene volcanic rocks from the Mojave Desert of southern California. Because these rocks contain a large component of recycled crust, their isotopic patterns can be used to study pre‐Miocene crustal structure which has been otherwise obscured and distorted by Mesozoic magmatism. Initial whole rock ⁸⁷Sr/⁸⁶Sr ratios (r_i) increase and δ¹⁸O values of silicic magmas decrease with distance inland; r_i also increases with SiO₂, indicating contamination by radiogenic crustal rocks. Initial ⁸⁷Sr/⁸⁶Sr ratios in the most primitive basalts are high (0.7045–0.7095), indicating derivation from an enriched mantle source. Correlations of r_i and δ¹⁸O with longitude indicate an eastward change in the nature of the contaminant. Silicic rocks have r_i and δ¹⁸O of 0.705–0.707 and 9–11‰, respectively, in the western and central Mojave Desert, and 0.708–0.710 and 7–8‰ near the Colorado River. High δ¹⁸O values of phenocrysts in rhyolites from the western Mojave Desert indicate that these rocks were derived from a high δ¹⁸O (>10‰) source. The most likely candidate for this material is underthrust metamorphic rocks of the Mesozoic‐Tertiary subduction complex (e.g., Rand‐Pelona‐Orocopia schist and related lithologies). This implies that some of the North American lithospheric mande was stripped from the western Mojave Desert during Mesozoic‐Paleogene subduction. The smoothness of the eastward increase in r_i constrains models for the tectonic evolution of southern California because no discontinuities corresponding to any of several proposed zones of pre‐Tertiary rifting or faulting are present.