New World monkeys (NWM) display substantial variation (two orders of magnitude) in body size. Despite this, variation in skull size and associated shape show a conserved allometric relationship, both within and between genera. Maximum likelihood estimates of quantitative ancestral states were used to compare the direction of morphological differentiation with the phenotypic (p_max) and genetic (g_max) lines of least evolutionary resistance (LLER). Diversification in NWM skulls occurred principally along the LLER defined by size variation. We also obtained measures of morphological amount and pace of change using our skull data together with published genetic distances to test whether the LLER influenced the amount and pace of diversification. Moreover, data on an ecological factor (diet) was obtained from the literature and used to test the association of this niche-related measure with the morphological diversification. Two strategies were used to test the association of LLER with the morphological and dietary amount and pace of change, one focusing on both contemporary genera and maximum likelihood reconstructed ancestors and the other using only the 16 contemporary genera in a phylogenetic comparative analysis. Our results suggest that the LLER influenced the path, amount, and pace of morphological change. Evolution also occurred away from the LLER in some taxa but this occurred at a slower pace and resulted in a relatively low amount of morphological change. We found that longer branch lengths (time) are associated with larger differences in p_max orientation. However, on a macroevolutionary scale there is no such trend. Diet is consistently associated with both absolute size differences and morphological integration patterns, and we suggest that this ecological factor might be driving adaptive radiation in NWM. Invasion of diet-based adaptive zones involves changes in absolute size, due to metabolic and foraging constraints, resulting in simple allometric skull diversification along the LLER. While it is clear that evolutionary change occurred along the LLER, it is not clear whether this macroevolutionary pattern results from a conservation of within-population genetic covariance patterns or long-term adaptation along a size dimension or whether both constraints and selection were inextricably involved.