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This paper describes the GISS‐E2.1 contribution to the Coupled Model Intercomparison Project, Phase 6 (CMIP6). This model version differs from the predecessor model (GISS‐E2) chiefly due to parameterization improvements to the atmospheric and ocean model components, while keeping atmospheric resolution the same. Model skill when compared to modern era climatologies is significantly higher than in previous versions. Additionally, updates in forcings have a material impact on the results. In particular, there have been specific improvements in representations of modes of variability (such as the Madden‐Julian Oscillation and other modes in the Pacific) and significant improvements in the simulation of the climate of the Southern Oceans, including sea ice. The effective climate sensitivity to 2 × CO2 is slightly higher than previously at 2.7–3.1°C (depending on version) and is a result of lower CO2 radiative forcing and stronger positive feedbacks. Plain Language Summary: This paper describes the latest iteration of the National Aeronautics and Space Administration (NASA) Goddard Institute for Space Studies (GISS) climate model, which will be used for understanding historical climate change and to make projections for the future. We compare the model output to a wide range of observations over the recent era (1979–2014) and show that there has been a significant increase in how well the model performs compared to the previous version from 2014, particularly in the Southern Ocean, though some persistent biases remain. The model has a temperature response to the increase of carbon dioxide that is slightly higher than previous versions but is well within the range expected from observational and past climate constraints. Key Points: GISS‐E2.1 is an updated climate model version for use within the CMIP6 projectAtmospheric composition is calculated consistently in all model versionsResults demonstrate a significant improvement in skill in a climate model without changes to atmospheric resolution [ABSTRACT FROM AUTHOR]