The Juan Fernandez Archipelago is a global biodiversity hotspot, where 67% of plant species are endemic, but competition with invasive plants threatens many native plant species with extinction. Murtilla Ugni molinae is a prevalent invasive plant in the archipelago which displaces native vegetation. This study aimed to determine an efficient one-time control method for murtilla that required little or no follow-up. We used an adaptive management framework to conduct chemical control trials of murtilla in order to identify an effective treatment. Eight different combinations of chemical treatments and manual cutting were tested in four trials between 2015 and 2017. The herbicides Rango (glyphosate) and Garlon 4 (triclopyr) were tested along with a surfactant, an emulsifier, ammonium sulphate and urea. Cutting stems at the base followed by stump application of triplocyr proved ineffective. All other treatments used foliar spraying. The most effective treatment was a foliar application of 3% triclopyr, 2% glyphosate and 15 g/l of urea diluted in water, which completely eliminated murtilla in 12 months. This treatment can be used for the control of murtilla over large areas and may also be useful to control other invasive shrubs that have leaves with thick cuticles resistant to herbicide absorption.