Family farms are facing unprecedented challenges with low commodity prices and high input costs, combined with regulatory obstacles that threaten the availability and practical use of pesticides. Ensuring that U.S. agriculture has access to economically effective and safe pest management tools is paramount for the nation and the world as farmers produce safe and affordable food, feed, fiber, and fuel. Field experiments in squash crops were carried out to assess the weed control effectiveness and economic value of a standard herbicide program compared to six nonchemical alternatives. The alternatives included 1) cultivating squash fields multiple times with a sweep plow; 2) cultivating fields multiple times with a tine weeder; 3 and 4) hand weeding to supplement plow or tine weeding efforts to achieve 75% weed control; and 5 and 6) hand weeding to supplement plow or tine weeding to achieve 95% weed control. When herbicides were applied, 98% to 99% control of Palmer amaranth, large crabgrass, and wild radish was achieved at a cost of US$104 ha−1 for the season. Cultivation (with a tine weeder or plow) provided only 36% to 64% control of each weed at a cost of $144 to $207 ha−1, and yielding 83% to 85% less squash than when herbicides were applied. Supplementing cultivation with 9 to 13 h of hand weeding per hectare achieved approximately 75% control, resulting in weed control costs ranging from $916 to $1,073 ha−1, with 40% to 47% less squash fruit harvested than when herbicides were applied. To achieve 95% weed control, 92 to 98 h ha−1 of hand weeding was required, with yields being comparable to those when herbicides were applied but weed control costs ranged from $8,344 to $8,527 ha−1, an increase of 80 to 82 times above the herbicide option. This experiment demonstrates how plant protection efforts can increase crop yield and quality while reducing costly inputs, thus improving the likelihood of safe, affordable, and sustainable food production.