Control of early-emerging weeds is essential to protect the yield potential of maize. An understanding of the physiological changes that occur as a result of weed interference is required to address variability in yield loss across sites and years. Field trials were conducted at the University of Guelph (UG), the Ohio State University (OSU), and Colorado State University (CSU) during 2009 and 2010. There were six treatments (season-long weedy and weed-free, and weed control at the 1st-, 3rd-, 5th-, and 10th-leaf-tip stages of maize development) and 20 individual plants per plot were harvested at maturity. We hypothesized that, as weed control was delayed, weed interference in the early stages of maize development would increase plant-to-plant variability in plant dry-matter accumulation, which would result in a reduction of grain yield at maturity. The onset of the critical period for weed control (CPWC) occurred on average between the third and fifth leaf tip stages of development (i.e., V1 to V3, respectively). Rate of yield loss following the onset of the CPWC ranged from 0.05 MG ha−1 d−1 at UG 2009 to 0.22 MG ha−1 d−1 at CSU 2010 (i.e., 0.5 and 1.6% d−1, respectively). On average, reductions in kernel number per plant accounted for approximately 65% of the decline in grain yield as weed control was delayed. Biomass partitioning to the grain was stable through early weed removal treatments, increased and peaked at the 10th-leaf-tip time of control, and decreased in the season-long weedy treatment. Plant-to-plant variability in dry matter at maturity and incidence of bareness increased as weed control was delayed. As weed control was delayed, the contribution of plant-to-plant variability at maturity to the overall yield loss was small, relative to the decline of mean plant dry matter.