Waterhemp (Amaranthus tuberculatus) has become a significant management challenge for soybean growers in the United States and recently in New York. This project characterized herbicide resistance across 23 populations in NY State and quantified resistance levels in two populations. Greenhouse screening with field-use rate showed multiple herbicide resistance to atrazine, chlorimuron + thifensulfuron, glyphosate, and mesotrione. Dose-response assays confirmed high level of resistance to those herbicides. Complementary field trials evaluating PRE, POST, and PRE followed by POST programs demonstrated that systems incorporating an effective soil-residual herbicide followed by timely POST herbicide applications provided the most consistent season-long control of waterhemp and minimized seedbank replenishment. This study documented the first case of multiple-herbicide resistance waterhemp in NY and evaluated PRE and POST programs that can be incorporated into management strategies to effectively control waterhemp.