Summary Due to its phenomenal growth requiring neither nitrogen fertilizer nor arable land and its biomass composition, the mosquito fern Azolla is a candidate crop to yield food, fuels and chemicals sustainably. To advance Azolla domestication, we research its dissemination, storage and transcriptome. Methods for dissemination, cross‐fertilization and cryopreservation of the symbiosis Azolla filiculoides–Nostoc azollae are tested based on the fern spores. To study molecular processes in Azolla including spore induction , a database of 37 649 unigenes from RNA seq of microsporocarps, megasporocarps and sporophytes was assembled, then validated. Spores obtained year‐round germinated in vitro within 26 d. In vitro fertilization rates reached 25%. Cryopreservation permitted storage for at least 7 months. The unigene database entirely covered central metabolism and to a large degree covered cellular processes and regulatory networks. Analysis of genes engaged in transition to sexual reproduction revealed a FLOWERING LOCUS T ‐like protein in ferns with special features induced in sporulating Azolla fronds. Although domestication of a fern–cyanobacteria symbiosis may seem a daunting task, we conclude that the time is ripe and that results generated will serve to more widely access biochemicals in fern biomass for a biobased economy.