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Observational records of meteorological and chemical variables are imprinted by an unknown combination of anthropogenic activity, natural forcings, and internal variability. With a 15-member initial-condition ensemble generated from the CESM2-WACCM6 chemistry-climate model for 1950–2014, we extract signals of anthropogenic (‘forced’) change from the noise of internally arising climate variability on observed tropospheric ozone trends. Positive trends in free tropospheric ozone measured at long-term surface observatories, by commercial aircraft, and retrieved from satellite instruments generally fall within the ensemble range. CESM2-WACCM6 tropospheric ozone trends are also bracketed by those in a larger ensemble constructed from five additional chemistry-climate models. Comparison of the multi-model ensemble with observed tropospheric column ozone trends in the northern tropics implies an underestimate in regional precursor emission growth over recent decades. Positive tropospheric ozone trends clearly emerge from 1950 to 2014, exceeding 0.2 DU yr⁻¹at 20–40 N in all CESM2-WACCM6 ensemble members. Tropospheric ozone observations are often only available for recent decades, and we show that even a two-decade record length is insufficient to eliminate the role of internal variability, which can produce regional tropospheric ozone trends oppositely signed from ensemble mean (forced) changes. By identifying regions and seasons with strong anthropogenic change signals relative to internal variability, initial-condition ensembles can guide future observing systems seeking to detect anthropogenic change. For example, analysis of the CESM2-WACCM6 ensemble reveals year-round upper tropospheric ozone increases from 1995 to 2014, largest at 30 S–40 N during boreal summer. Lower tropospheric ozone increases most strongly in the winter hemisphere, and internal variability leads to trends of opposite sign (ensemble overlaps zero) north of 40 N during boreal summer. This decoupling of ozone trends in the upper and lower troposphere suggests a growing prominence for tropospheric ozone as a greenhouse gas despite regional efforts to abate warm season ground-level ozone.