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The Katla volcano is a bimodal caldera complex within Iceland's basalt-dominated Eastern Volcanic Zone. To unravel the petrogenesis of silica-rich rocks from Katla, we provide new δ¹⁸O values for almost 60 basaltic, intermediate, and high-silica eruptive rocks, including a number of partially melted felsic xenoliths. The basaltic samples display a range in bulk-rock δ¹⁸O values from +4.3 to +8.5‰ (n = 17) and the sparse intermediate samples from +4.1 to +5.9‰ (n = 3). In turn, silicic rock samples and feldspar separates range from +2.7 to +6.4‰ (n = 38), whereas felsic xenoliths yield the lowest values from −4.9 to −2.3‰ (n = 4). The majority (95%) of the Katla silicic volcanics have δ¹⁸O values below typical MORB (i.e., ≤5.0‰), ruling out an origin via closed-system fractional crystallization from the basaltic magmas. We utilized the new δ¹⁸O values to model possible assimilation and fractional crystallization (AFC) scenarios. The results indicate an early stage of FC/AFC at deep- to mid-crustal levels, followed by assimilation of low-δ¹⁸O hydrothermally altered sub-volcanic materials similar to the low-δ¹⁸O felsic xenoliths at shallow crustal levels. Such a two-stage magma evolution is consistent with available geophysical and geobarometry studies at Katla, indicating mid- to deep-crustal and shallow-crustal magma domains. Importantly, mafic rocks dominantly show MORB-like δ¹⁸O values, whereas low δ¹⁸O values occur essentially in silicic rocks only. This implies that the low-δ¹⁸O values at Katla are imposed by interaction with the Icelandic crust rather than reflecting low δ¹⁸O mantle sources.