Field trials were conducted at the Teaching and Research Farm of the Kwara State University, Nigeria, during the 2013 and 2014 cropping seasons. The aim was to determine the effect of periods of weed interference on weed infestation, maize growth and yield. The experiment consisted of 10 treatments, namely, plots initially kept weed-free for 3, 6, 9 and 12 Weeks. After Sowing (WAS) and subsequently left weedy until harvest and plots initially left weedy for 3, 6, 9 and 12 Weeks. After Sowing (WAS) and subsequently kept weed-free till harvest. There were two control plots, one left weedy and the other kept weed–free till harvest. The treatments were laid out in randomized complete block design (RCBD) and replicated three times. Parameters measured were weed dry weight, maize plant height, leaf area, number of leaves/plant, cob weight, number of kernel rows/cob, 100 seed weight and grain yield. Results show that weed interference in maize for 6WAS and beyond significantly depressed growth parameters and grain yield. Plots which received weed interference for 3WAS produced significantly higher yield which was comparable to the maximum. Therefore, it is understood from the current studies that maize plot be kept weed-free between 3 and 6 WAS which is the critical period of weed interference, in order to get optimal yield.