A field experiment was conducted during February to July 2024 at Pandit Jawaharlal Nehru College of Agriculture and Research Institute, Karaikal, Puducherry, to study the effect of herbicide application using Unmanned Aerial Vehicle (UAV) on the diverse weed flora, cotton growth, yield and economics. The experiment consisted of seven treatments, viz. pre-emergence application (PE) of pendimethalin 1.0 kg/ha using UAV with spray volume of 25, 37.5, 50 L/ha; pendimethalin 1.0 kg/ha PE using knapsack sprayer with spray volume of 500 L/ha water, inter-cultivation twice at 20 and 45 days after seeding (DAS), inter-cultivation twice followed by (fb) manual weeding at 60 DAS and unweeded control. A randomized block design with three replications was used. The grasses were dominant in the experimental plot, with 57.8 % relative density of Echinochloa colona. Pendimethalin 1.0 kg/ha on 3 DAS using UAV with a spray volume of 37.5 L/ha resulted in greater reduction in total weed density and biomass with better cotton growth (plant height), yield parameters (number of bolls/plant, boll weight), yield, higher net return and benefit:cost ratio. Uncontrolled weeds caused 87.7 % yield loss in summer cotton of the coastal deltaic ecosystem.