According to the invention, there is provided seed and plants of the corn variety designated I180421. This invention thus relates to the plants, seeds and tissue cultures of the variety I180421, and to methods for producing a corn plant produced by crossing a corn plant of variety I180421 with itself or with another corn plant, such as a plant of another variety. This invention further relates to corn seeds and plants produced by crossing plants of variety I180421 with plants of another variety, such as another inbred line, and to crosses with related species. This invention further relates to the inbred and hybrid genetic complements of plants of variety I180421, and also to the SSR profiles of corn variety I180421.