The introduction of herbicide resistant Palmer amaranth and waterhemp began in 2010 and spread rapidly across Kentucky's soybean production regions during the past 8 years. Most of these introduced populations are resistant to glyphosate (EPSPS enzyme) and ALS type herbicides. Populations of Palmer amaranth in west Kentucky and a number of waterhemp populations across Kentucky were confirmed by genetic lab analysis to also have resistance to foliar applied fomesafen (PPO type herbicide). Field trials were conducted in 2016 and 2017 near Barlow and Paris, KY to investigate various soil-applied followed by postemergence herbicide combinations for their effectiveness on these resistant weed populations so that best management strategies can be developed for control of these complex weed populations with multiple sites of herbicide resistance. Soil residual (PRE) herbicide treatments applied at planting that contained three-way mixtures of pyroxasulfone + flumioxazin + chlorimuron (ie. Fierce XLT) or S-metolachlor + fomesafen + metribuzin (ie. Intimidator) provided the best early season control (>80%) of Palmer amaranth and/or waterhemp. Soil-applied herbicide products with S-metolachlor + metribuzin (ie. Boundary) and S-metolachlor + sulfrentrazone (ie. Broadaxe XC) were less effective. These results are similar to a field trial conducted in 2016 that indicated that soil residual herbicide treatments containing at least 3 different sites of herbicidal activity achieved a much greater level of early season control compared to herbicides with only 1 or 2 sites of action. When an effective soil residual herbicide such as Fierce XLT or Intimidator was followed by a timely postemergence (POST) herbicide treatment >80% control was maintained through mid season. Postemergence treatments containing dicamba (ie. Xtendimax) + glyphosate, 2,4-D + glyphosate (ie. Enlist Duo), and glufosinate (ie. Liberty) following a soil-applied treatment at planting achieved the most effective season-long control. These results indicate that herbicide treatments with PRE/POST combinations with 3 to 4 sites of herbicidal activity are best for combating herbicide resistant populations of Palmer amaranth and waterhemp.