Microplastic (MP) pollution poses a global threat to urban and rural environments and can have negative effects on a range of organisms. Mosquito larvae often breed in water contaminated with MPs, and given their important role as disease vectors, understanding the effects of larval exposure to MPs is critical for understanding the potential impact on their life history traits and subsequent methods for their control. Here, we have exposed first instar larvae of Anopheles gambiae s.s. to environmentally realistic concentrations of PET microplastics (1.0–7.5 μm) and a sub-lethal dose of insecticide mixed with microplastics, and quantified survival, development, and susceptibility of larvae over six generations. Adult mosquitoes from larvae exposed to these treatments were subsequently tested for insecticide resistance. Exposure to MPs decreased larval survival rates compared to the control; however, over six generations of exposure, survival rates significantly increased. Similarly, there was a higher survival rate of those larvae exposed to MPs mixed with insecticide compared to those exposed to just the insecticide, and survival increased further over the six generations. For the adult mosquito susceptibility tests, knockdown times (KDTs) indicated some level of insecticide tolerance when larvae had been previously exposed to MPs and insecticides. This is the first study demonstrating the selection of insecticide tolerance in adult mosquitoes after consecutive generations of larval exposures to varying concentrations of MPs. Therefore, field-scale studies are now urgently required to quantify whether larval insecticides are less effective at controlling mosquitoes in breeding sites commonly polluted with MPs.