Seventeen putative resistant late watergrass populations [Echinochloa phyllopogon (Stapf.) Koso-Pol.; syn.: Echinochloa oryzicola (Vasinger) Vasinger] originating from rice (Oryza sativa L.) monoculture fields in northern Greece were examined for possible evolution of multiple resistance to acetolactate synthase (ALS) and acetyl-CoA carboxylase (ACCase) inhibitors and auxin herbicides in rate–response pot assays. Most of the populations were highly cross-resistant to the ALS-inhibiting herbicides bispyribac-Na, imazamox, penoxsulam, and nicosulfuron + rimsulfuron, whereas three of them were also multiple resistant to both ALS and the auxin mimic quinclorac. In addition, two E. phyllopogon populations were found to be multiple resistant to the ALS and ACCase inhibitors cycloxydim, cyhalofop-butyl, profoxydim, and quizalofop-P-ethyl. Amplification and sequencing of the ACCase gene fragment from eight surviving profoxydim-treated plants of the two multiple-resistant E. phyllopogon populations to ALS- and ACCase-inhibiting herbicides, revealed an Ile to Leu substitution at codon 1781 of the ACCase enzyme. However, amplification and sequencing of the ALS gene fragment in the same E. phyllopogon plants sequenced for ACCase revealed a Trp to Leu substitution at codon 574 of the ALS enzyme in three out of the eight sequenced plants. These results strongly support the evidence of coexisting E. phyllopogon multiple target-site resistance to ALS and ACCase inhibitors, which is reported for the first time.