Early season crop-weed interactions during a critical weed-free period (CWFP) influence corn growth that commonly results in reduced yield. Yield loss is not mitigated by weed removal after the CWFP, hence, weeds cause an irreversible negative impact on growth and development during the CWFP.  However, mechanisms that bring about yield loss during the CWFP are not well understood.  This study determined the critical weed-free period in corn and associated changes in gene expression (transcriptome analysis), and examined the impact of early-season weed, nitrogen (N), and light stresses on growth and development of corn.  Plant biomass, leaf area, plant height, chlorophyll content, reflectance and differential gene expression were measured at several growth stages.  Negative impacts of N stress through V8 on biomass and leaf area were minimal (15-20%) compared with other stress factors. Shade-stressed corn demonstrated a 60% reduction in biomass, 50% reduction in leaf area, and was 44% shorter than non-stressed controls at V2.  Corn biomass and leaf area were progressively reduced up to 70% at the V8 stage and was 20-23% shorter in shade stressed corn.   Weed-stressed corn had reductions of 60% for biomass and 52% for leaf area at V8. Yield losses were 22% for N-stressed corn, about 15% for shade-stressed corn, and 33% for weed-stressed corn if not controlled until V8. Gene set enrichment analysis indicated photosynthetic processes were down regulated if weeds were present during CWFP. Examples of the genes that were preferentially down-regulated as early as V2 were Rubisco, and Pepc. These photosynthetic gene expressions remained down-regulated even if weeds were removed after the CWFP. These data indicate that N, shade, and weed stresses differ in mechanism.  Weed-stress during CFWP permanently limits photosynthetic capabilities even after removal and may be an important factor contributing to end-of-season yield loss.