King John VI of Portugal created the order on 4 November 1801 in honour of Queen Saint Isabel, consort of Portuguese King Denis I, investing his wife Carlota Joaquina as Grand Mistress of the order.

The order, which was considered dynastic, continued to be bestowed by King Manuel II of Portugal, who in exile also awarded it to his wife.

The Duchess of Braganza is the current Grand Mistress and, besides honouring Portuguese noblewomen on the Saint's feast day, celebrated each year on 4 July at the Monastery of Santa Clara-a-Nova in Coimbra, the Royal House has, since 2000, bestowed it on various queens, princesses and women dedicated to the support of Portuguese charities.

On the accompanying crowned medallion is a picture of the Queen Saint giving money to a poor man.

The annual ceremonial induction of Noble ladies of Saint Isabel takes place in the Convent of Santa Clara in Coimbra, on 4 July.