Following six consecutive annual applications of imazaquin in combination with trifluralin or pendimethalin to several soybean fields on the Delmarva Peninsula, unacceptable smooth pigweed control was observed. Field and greenhouse studies were conducted to determine if this population of smooth pigweed was resistant to imazaquin and other herbicides. In field research, imazaquin and imazethapyr gave complete control of the susceptible (S) population while providing no control of the resistant (R) population; pyrithiobac controlled 99 and 90% of the R and S populations, respectively. Pendimethalin, metribuzin, MON-12000, and flumiclorac gave less than 75% control of both S and R populations. Chlorimuron, primisulfuron, CGA-152005, and lactofen gave above 75% control, and thifensulfuron and nicosulfuron gave above 90% control of both S and R populations. Seeds were collected from the R and S smooth pigweed populations for research in the greenhouse. Greenhouse studies confirmed high levels of resistance to imazaquin and imazethapyr and low levels of cross-resistance to rimsulfuron and chlorimuron in the R population. Susceptibility of the R population to nicosulfuron, thifensulfuron, pyrithiobac, and pendimethalin was comparable to that of the S population.