Italian ryegrass [Lolium perenne L. spp. multiflorum (Lam.) Husnot] is a troublesome weedy species in many regions of California. Its control has been chiefly dependent on herbicides due to their effectiveness and practicality and, as result, herbicide-resistant populations have been selected. Poor control of a population of L. multiflorum with paraquat was recently reported in a prune orchard in Hamilton City, CA. A series of experiments were carried out to characterize the response of this population to several POST herbicides, study the mechanisms of resistance, and investigate alternative chemical management options in tree crops. A known susceptible (S) and the suspected resistant population (PRHC) were subjected to greenhouse dose–response experiments with clethodim, fluazifop-P-butyl, glufosinate, glyphosate, paraquat, pyroxsulam, rimsulfuron, and sethoxydim. A 310-bp fragment of the EPSPS gene containing position 106 was sequenced from PRHC and S. Field experiments were carried out in a prune orchard with PRE herbicides commonly used by perennial crop growers in California. Greenhouse dose–response experiments confirmed that PRHC is resistant to paraquat, as well as multiply resistant to clethodim and glyphosate. The EPSPS gene of PRHC is heterozygous for glyphosate resistance at position 106, where one allele exhibited proline substituted by serine and the other by alanine. Field experiments with PRE herbicides indicated that tank mixes containing indaziflam and flumioxazin can provide adequate L. multiflorum control up to 150 d after treatment. Poor weed management practices, such as overreliance on a single site of action, have frequently been associated with the selection of herbicide-resistant L. multiflorum populations around the world, and adequate herbicide-resistance management programs are necessary for growers to maintain economic sustainability even after evolution of herbicide-resistant weeds in their fields.