La Serenísima was established in 1929 by Antonino Mastellone, a cheese-maker from Sardinia who arrived in Argentina in 1925. Antonio and his brother Giuseppe Mastellone founded Hermanos Mastellone in General Rodríguez, a pampas city west of Buenos Aires, in 1927. La Serenísima became the first in Argentina to provide nutritional facts on each bottle. The company pioneered the sale of lactose-free milk in Argentina in 1984, became the market leader in the sale of yogurt and introduced cultured milk locally, in 1988. La Serenísima also introduced large-scale organic dairy farming in Argentina, in 1994, and became the first to fortify its products with iron sulfate.

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