Blessed milkthistle is considered to be a noxious weed in irrigated and rainfed areas of Pakistan due to its strong allelopathic effects on food crops. For sustainable wheat production, it is necessary to know the critical time for weed removal (CTWR) for blessed milkthistle to allow wheat growers to get maximum benefit from control of this weed. A field study was conducted in 2014 and 2015 at the College of Agriculture, University of Sargodha, Pakistan, to investigate the CTWR of blessed milkthistle in wheat. The field experiments were designed with seven treatments; weed free (control); 2, 3, 4, 5, and 6 wk after emergence (WAE); and weedy check. At 6 WAE, a significant reduction was noted in plant height (8% and 17%), number of productive tillers per square meter (16% and 16%), spike length (23% and 54%), grains per spike (13% and 34%), 1,000-grain weight (14% and 37%), grain yield (20% and 21%), and biological yield (24% and 50%) compared with control (weed-free plots) during 2014 and 2015, respectively. The logistic model supports the field study results and suggests that blessed milkthistle’s CTWR for wheat is 1 to 5 WAE based on acceptable yield losses of 5% to 15% during both years. The experimental results and logistic model indicate that blessed milkthistle should be controlled within 1 to 5 WAE to get better wheat crop harvests without compromising farmers’ profits. To our knowledge, this is the first study ever in Pakistan regarding the CTWR in terms of WAE of blessed milkthistle and could help other scientists create weed control strategies for other areas of the country.