The cotton mealybug, Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae) has gained recognition as a key pest due to its invasive nature throughout the world. The P. solenopsis has a wide range of host plants and damages the cotton crop in various parts of the world. In view of the economic importance of this pest, a study on selection, inheritance and mechanism of spinosad resistance was conducted on P. solenopsis. Selection of field collected P. solenopsis for seven generations with spinosad resulted in a high resistance ratio of 282.45-fold. Genetic studies of spinosad resistance in P. solenopsis indicated that maternal effects are not involved in spinosad resistance ; and resistance development is an autosomal and incompletely dominant trait. The number of genes involved in spinosad resistance was determined to be more than one, suggesting that resistance is controlled by multiple loci. The realized heritability (h 2) value for spinosad resistance was 0.94. Synergism bioassays of spinosad with piperonyl butoxide and S,S,S-tributyl phosphorotrithioate showed that spinosad resistance in P. solenopsis could be due to esterase only. The study provides the basic information for implementation of effective resistance management strategies to control P. solenopsis.