The invention relates to the seeds of soybean cultivar S080100, to the plants of soybean S080100, to plant parts of soybean cultivar S080100, and to methods for producing a soybean plant produced by crossing soybean cultivar S080100 with itself or with another soybean variety. The invention also relates to methods for producing a soybean plant containing in its genetic material one or more transgenes and to the transgenic soybean plants and plant parts produced by those methods. This invention also relates to soybean cultivars, or breeding cultivars, and plant parts derived from soybean variety S080100, to methods for producing other soybean cultivars, lines or plant parts derived from soybean cultivar S080100, and to the soybean plants, varieties, and their parts derived from use of those methods. The invention further relates to hybrid soybean seeds, plants, and plant parts produced by crossing the cultivar S080100 with another soybean cultivar.