Abstract The Colorado State University (CSU) Multiscale Modeling Framework (MMF) is a new type of general circulation model (GCM) that replaces the conventional parameterizations of convection, clouds, and boundary layer with a cloud-resolving model (CRM) embedded into each grid column. The MMF has been used to perform a 19-yr-long Atmospheric Model Intercomparison Project–style simulation using the 1985–2004 sea surface temperature (SST) and sea ice distributions as prescribed boundary conditions. Particular focus has been given to the simulation of the interannual and subseasonal variability. The annual mean climatology is generally well simulated. Prominent biases include excessive precipitation associated with the Indian and Asian monsoon seasons, precipitation deficits west of the Maritime Continent and over Amazonia, shortwave cloud effect biases west of the subtropical continents due to insufficient stratocumulus clouds, and longwave cloud effect biases due to overestimation of high cloud amounts, especially in the tropics. The geographical pattern of the seasonal cycle of precipitation is well reproduced, although the seasonal variance is considerably overestimated mostly because of the excessive monsoon precipitation mentioned above. The MMF does a good job of reproducing the interannual variability in terms of the spatial structure and magnitude of major anomalies associated with El Niño–Southern Oscillation (ENSO). The subseasonal variability of tropical climate associated with the Madden–Julian oscillation (MJO) and equatorially trapped waves are particular strengths of the simulation. The wavenumber–frequency power spectra of the simulated outgoing longwave radiation (OLR), precipitation rate, and zonal wind at 200 and 850 mb for time scales in the range of 2–96 days compare very well to the spectra derived from observations, and show a robust MJO and Kelvin and Rossby waves with phase speeds similar to those observed. The geographical patterns of the MJO and Kelvin wave–filtered OLR variance for summer and winter seasons are well simulated; however, the variances tend to be overestimated by as much as 50%. The observed seasonal and interannual variations of the strength of the MJO are also well reproduced. The physical realism of the simulated marine stratocumulus clouds is demonstrated by an analysis of the composite diurnal cycle of cloud water content, longwave (IR) cooling, vertical velocity variance, rainfall, and subcloud vertical velocity skewness. The relationships between vertical velocity variance, IR cooling, and negative skewness all suggest that, despite the coarse numerical grid of the CRM, the simulated clouds behave in a manner consistent with the understanding of the stratocumulus dynamics. In the stratocumulus-to-cumulus transition zone, the diurnal cycle of the inversion layer as simulated by the MMF also bears a remarkable resemblance to in situ observations. It is demonstrated that in spite of the coarse spacing of the CRM grid used in the current version of MMF, the bulk of vertical transport of water in the MMF is carried out by the circulations explicitly represented on the CRM grid rather than by the CRM’s subgrid-scale parameterization.