A new macroseismic intensity prediction equation is derived for the central and eastern United States and is used to estimate the magnitudes of the 1811–1812 New Madrid, Missouri, and 1886 Charleston, South Carolina, earthquakes. This work improves upon previous derivations of intensity prediction equations by including additional intensity data, correcting magnitudes in the intensity datasets to moment magnitude, and accounting for the spatial and temporal population distributions. The new relation leads to moment magnitude estimates for the New Madrid earthquakes that are toward the lower range of previous studies. Depending on the intensity dataset to which the new macroseismic intensity prediction equation is applied, mean estimates for the 16 December 1811, 23 January 1812, and 7 February 1812 mainshocks, and 16 December 1811 dawn aftershock range from 6.9 to 7.1, 6.8 to 7.1, 7.3 to 7.6, and 6.3 to 6.5, respectively. One‐sigma uncertainties on any given estimate could be as high as 0.3–0.4 magnitude units. We also estimate a magnitude of 6.9±0.3 for the 1886 Charleston, South Carolina, earthquake. We find a greater range of magnitude estimates when also accounting for multiple macroseismic intensity prediction equations. The inability to accurately and precisely ascertain magnitude from intensities increases the uncertainty of the central United States earthquake hazard by nearly a factor of two. Relative to the 2008 national seismic hazard maps, our range of possible 1811–1812 New Madrid earthquake magnitudes increases the coefficient of variation of seismic hazard estimates for Memphis, Tennessee, by 35%–42% for ground motions expected to be exceeded with a 2% probability in 50 years and by 27%–35% for ground motions expected to be exceeded with a 10% probability in 50 years.