We present constraints on cosmological parameters based on a sample of Sunyaev–Zel’dovich-selected (SZ-selected) galaxy clusters detected in a millimeter-wave survey by the Atacama Cosmology Telescope. The cluster sample used in this analysis consists of nine optically confirmed high-mass clusters comprising the highsignificance end of the total cluster sample identified in 455 deg² of sky surveyed during 2008 at 148 GHz. We focus on the most massive systems to reduce the degeneracy between unknown cluster astrophysics and cosmology derived from SZ surveys.We describe the scaling relation between cluster mass and SZ signal with a four-parameter fit. Marginalizing over the values of the parameters in this fit with conservative priors gives σ₈ = 0.851 ± 0.115 and ω = −1.14 ± 0.35 for a spatially flat wCDM cosmological model with Wilkinson Microwave Anisotropy Probe (WMAP) seven-year priors on cosmological parameters. This gives a modest improvement in statistical uncertainty over WMAP seven-year constraints alone. Fixing the scaling relation between the cluster mass and SZ signal to a fiducial relation obtained from numerical simulations and calibrated by X-ray observations, we find σ₈ = 0.821 ± 0.044 and ω = −1.05 ± 0.20. These results are consistent with constraints from WMAP7 plus baryon acoustic oscillations plus Type Ia supernova which give σ₈ = 0.802 ± 0.038 and ω = −0.98 ± 0.053. A stacking analysis of the clusters in this sample compared to clusters simulated assuming the fiducial model also shows good agreement. These results suggest that, given the sample of clusters used here, both the astrophysics of massive clusters and the cosmological parameters derived from them are broadly consistent with current models.