Soybean is the most important oilseed crop that is grown in India. Horse purslane (Trianthema portulacastrum L.) infests soybean heavily, causing enormous yield losses and threatening the sustainability of the soybean production system. Information on the interference and economic threshold of horse purslane will be useful for the effective management of horse purslane in soybean. This will lead to the rationalization of herbicide use and the reduction of herbicide input into the environment. It was observed in this study that “a composite stand of weeds including horse purslane”, and 200 horse purslane plants per m2 were equally competitive to soybean. These two treatments resulted in a higher dry weight, growth rate, and uptake of N, P, and K by the weeds and/or horse purslane, compared to the other treatments. They caused more reductions in soybean growth (dry weight, height, crop growth rate, net assimilation rate, and leaf area index) and resulted in a more significant yield reduction than did the other treatments. The weed density–crop yield and the relative leaf area–crop yield models were found to be equally effective in simulating soybean yield losses in relation to a wide range of horse purslane densities and the regression equations were a good fit. The quadratic equations revealed that a density of approximately six, five, and four horse purslane plants per m2 would be the economic threshold levels of horse purslane in soybean cultivation, when considering the 70, 80, and 90% horse purslane control efficiencies, respectively, of the herbicide, lactofen.