Great Mullein is a biennial and generally requires winter dormancy before it can flower. This dormancy is linked to starch degradation activated by low temperatures in the root, and gibberellin application bypasses this requirement. Seeds germinates almost solely in bare soil, at temperatures between 10 °C and 40 °C. While they can germinate in total darkness if proper conditions are present (tests give a 35% germination rate under ideal conditions), in the wild, they in practice only do so when exposed to light, or very close to the soil surface, which explains the plant's habitat preferences. While it can also grow in areas where some vegetation already exists, growth of the rosettes on bare soil is four to seven times more rapid.
Seeds germinate in spring and summer. Those that germinate in autumn produce plants that overwinter if they are large enough, while rosettes less than 15 cm (5.9 in) across die in winter. After flowering the entire plant usually dies at the end of its second year, but some individuals, especially in the northern parts of the range, require a longer growth period and flower in their third year. Under better growing conditions, some individuals flower in the first year. Triennial individuals have been found to produce fewer seeds than biennial and annual ones. While year of flowering and size are linked to the environment, most other characteristics appear to be genetic.
A given flower is open only for a single day, opening before dawn and closing in the afternoon. Flowers are self-fecundating and protogynous (with female parts maturing first), and will self-pollinate if they have not been pollinated by insects during the day. While many insects visit the flowers, only some bees actually accomplish pollination. V. thapsus' flowering period lasts from June to August in most of its range, extending to September or October in warmer climates.