Semiconductor nanowires are routinely grown on high-priced crystalline substrates as it is extremely challenging to grow directly on plastics and flexible substrates due to high-temperature requirements and substrate preparation. At the same time, plastic substrates can offer many advantages such as extremely low price, light weight, mechanical flexibility, shock and thermal resistance, and biocompatibility. We explore the direct growth of high-quality III–V nanowires on flexible plastic substrates by metal-organic vapor phase epitaxy (MOVPE). We synthesize InAs and InP nanowires on polyimide and show that the fabricated NWs are optically active with strong light emission in the mid-infrared range. We create a monolithic flexible nanowire-based p–n junction device on plastic in just two fabrication steps. Overall, we demonstrate that III–V nanowires can be synthesized directly on flexible plastic substrates inside a MOVPE reactor, and we believe that our results will further advance the development of the nanowire-based flexible electronic devices.