Fall-applied residual and spring preplant burn-down herbicide applications are typically used to control winter annual weeds and may also provide early-season residual control of summer annual weed species such as giant ragweed. Field experiments were conducted from 2006 to 2008 in southern Illinois to (1) assess the emergence pattern of giant ragweed, (2) evaluate the efficacy of several herbicides commonly used for soil-residual control of giant ragweed, and (3) investigate the optimal application timing of soil-residual herbicides for control of giant ragweed. Six herbicide treatments were applied at four application timings: early fall, late fall, early spring, and late spring. Giant ragweed first emerged in mid- and late-March in 2007 and 2008, respectively. The duration of emergence varied by year, with 95% of emergence complete in late May of 2008, but not until early July in 2007. Giant ragweed emergence occurred more quickly in plots that received a fall application of glyphosate + 2,4-D compared with the nontreated. Fall-applied residual herbicides did not reduce giant ragweed emergence in 2007 when compared with the nontreated, with the exception of chlorimuron + tribenuron applied in late fall. Giant ragweed control from early- and late-spring herbicide applications was variable by year. In 2007, saflufenacil (50 and 100 g ai ha−1) and simazine applied in early spring reduced giant ragweed densities by 95% or greater through mid-May; however, in 2008, early-spring applications failed to reduce giant ragweed emergence in mid-April. The only treatments that reduced giant ragweed densities by > 80% through early July were late-spring applications of chlorimuron + tribenuron or saflufenacil at 100 g ha−1. Thus, the emergence patterns of giant ragweed in southern Illinois dictates that best management with herbicides would include late-spring applications of soil-residual herbicides just before crop planting and most likely requires subsequent control with foliar or soil-residual herbicides after crop emergence.