Replacement control technology is a sustainable strategy for the control of invasive weeds. Two consecutive years of field experiments were conducted in Xichang city to assess the ecological and economical possibility of replacement control of Eupatorium adenophorum (Spreng.) King & H.Rob. with maize. Four treatment groups were planted with maize at different densities after cutting E. adenophorum. Two reference groups were set by not treating and only cutting the aerial parts of E. adenophorum. All maize replacements in the “after tillage” treatments provided control effects of up to 100% and significantly reduced water and fertilizer use by E. adenophorum. Maize replacement provided a substantial economic benefit of up to 20,273.50 and 23,633.22 yuan/hm2 in two consecutive years and increased incomes. Evaluated in terms of niche theory, the large leaves as well as high plant cover assisted in effectively occupying the available niche and reduced light interception, seed germination and growth of E. adenophorum. This study provided a scientific basis for the sustainable and eco-friendly control of weeds by ecological methods.