This study reports oxygen isotope ratios determined by laser fluorination of mineral separates (mainly plagioclase) from basaltic andesitic to rhyolitic composition volcanic rocks erupted from the Lassen Volcanic Center (LVC), northern California. Plagioclase separates from nearly all rocks have δ¹⁸O values (6·1–8·4‰) higher than expected for production of the magmas by partial melting of little evolved basaltic lavas erupted in the arc front and back-arc regions of the southernmost Cascades during the late Cenozoic. Most LVC magmas must therefore contain high ¹⁸O crustal material. In this regard, the δ¹⁸O values of the volcanic rocks show strong spatial patterns, particularly for young rhyodacitic rocks that best represent unmodified partial melts of the continental crust. Rhyodacitic magmas erupted from vents located within 3·5 km of the inferred center of the LVC have consistently lower δ¹⁸O values (average 6·3‰ ± 0·1‰) at given SiO₂ contents relative to rocks erupted from distal vents (>7·0 km; average 7·1‰ ± 0.1‰). Further, magmas erupted from vents situated at transitional distances have intermediate values and span a larger range (average 6·8‰ ± 0·2‰). Basaltic andesitic to andesitic composition rocks show similar spatial variations, although as a group the δ¹⁸O values of these rocks are more variable and extend to higher values than the rhyodacitic rocks. These features are interpreted to reflect assimilation of heterogeneous lower continental crust by mafic magmas, followed by mixing or mingling with silicic magmas formed by partial melting of initially high ¹⁸O continental crust (∼9·0‰) increasingly hybridized by lower δ¹⁸O (∼6·0‰) mantle-derived basaltic magmas toward the center of the system. Mixing calculations using estimated endmember source δ¹⁸O values imply that LVC magmas contain on a molar oxygen basis approximately 42 to 4% isotopically heavy continental crust, with proportions declining in a broadly regular fashion toward the center of the LVC. Conversely, the δ¹⁸O values of the rhyodacitic rocks suggest that the continental crust in the melt generation zones beneath the LVC has been substantially modified by intrusion of mantle-derived basaltic magmas, with the degree of hybridization ranging on a molar oxygen basis from approximately 60% at distances up to 12 km from the center of the system to 97% directly beneath the focus region. These results demonstrate on a relatively small scale the strong influence that intrusion of mantle-derived mafic magmas can have on modifying the composition of pre-existing continental crust in regions of melt production. Given this result, similar, but larger-scale, regional trends in magma compositions may reflect an analogous but more extensive process wherein the continental crust becomes progressively hybridized beneath frontal arc localities as a result of protracted intrusion of subduction-related basaltic magmas.