Amaranthus palmeri (Palmer Amaranth) is a dioecious annual weed species, originating from the Southern USA, spreading rapidly beyond its original range into Europe and the Mediterranean region. In Israel, A. palmeri distribution has expanded quickly in recent years, with farmers reporting on weed control failure using acetolactate synthase (ALS) inhibitors. Furthermore, recent studies have documented glyphosate‐resistant cases from other countries in the region, such as Spain, Greece and Turkey. We conducted a survey in order to understand A. palmeri distribution and study the occurrence of herbicide resistance to both glyphosate and trifloxysulfuron in different fields across the country. According to our data, A. palmeri population locations are aligned with the major agricultural areas for summer field crops, including the Hula Valley, Jezreel Valley and the Southern Coastal Plain. Regarding herbicide responses, while several populations showed a reduced response to glyphosate, dose–response assays did not show resistance to the recommended labelled field rate. For the ALS inhibitor trifloxysulfuron, the survival percentage was very high, especially in the southern coastline region (77%). Four populations used for dose–response studies were highly resistant, surviving at four times the recommended labelled field rate of trifloxysulfuron (30 g a.i. ha−1). Sequencing of the ALS gene, Trp574 to Leu alteration in resistant populations was recorded in all populations. The high level of resistance observed in this study, alongside the target‐site mutation found in populations of A. palmeri, endangers the future use of ALS inhibitors in corn, cotton, and other summer crops grown in Israel.