The increasing interest in fine-grained blocks requires a deeper understanding of the impact of block size on urban vitality. To date, limited empirical tests of the underlying relationships at the city level have been conducted using the ordinary linear-squares method, assuming a linear relationship. However, urban vitality is a complex system, thus making the use of linear regressions unfeasible because the assumption of homogeneity of variance would be violated. Therefore, the constraint line method was introduced to deepen the understanding of the relationship between block size and urban vitality. This paper employed a kernel density estimation of small catering businesses, point of interest density, social media check-in density, and comment density as proxies of urban vitality. Wuhan is the largest megacity in Central China and has been selected for this case study. When the block size increased to almost 0.08 km2, the maximum kernel density estimation value decreased sharply from above 2.70 to 1.60; when the block size exceeded 0.30 km2, vitality values tended to decrease very slowly. The maximum urban vitality measured by the other three indicators dropped an order of magnitude when the block size increased to 0.06 km2, then gradually slowed down, and tended toward a plateau when the block size increased beyond 0.20. Therefore, the dynamic process can be divided into three phrases with multiple critical thresholds of block size. These are approximately 0.06, 0.08, and 0.20 km2 ranked from the best to worst. The study indicates that block size has a nonlinear and threshold effect on urban vitality by constraining the maximum urban vitality. In general, the positive effect of small block size over urban vitality was confirmed, and additionally, urban planners should propose urban planning schemes with smaller residential blocks below 0.06 km2.