The monastery was consecrated in 1721, after the Clares of Elisabethsdal in Boxtel were forced by the authorities to leave the Meierij of 's-Hertogenbosch. Megen, on the other hand, had a separate status within the Republic of the Netherlands and enjoyed religious freedom. The monastery was built on the site of the ruins of the castle of the Counts of Megen in 1720. The sisters received support from the Poor Clares in Hoogstraten.
In 1727, the Republic appropriated the income from the monastery, so the sisters had to look for new sources of income, such as the manufacture of quick salt and balm, and from 1766 a host bakery.
In 1798 the sisters were expelled by the French, but when the county was sold to the Batavian Republic in 1800, the monastery was allowed to function again. But in 1810 Megen was annexed by Napoleon and in 1812 the monasteries were ordered to be abolished.
Under the reign of King William I, after 1814, the monastery was not allowed to accept novices. However, 15 novices were secretly accepted. In 1840, under King William II, the oppression of monastic life disappeared. In 1876, Ammersoyen Castle in Ammerzoden was purchased, where a Poor Clare monastery was also founded. In 1896 the Poor Clares were able to buy back their monastery in Megen, which was formally owned by the State, and in 1898 a new monastery chapel was inaugurated.
In 1934, a monastery was founded in Cikurug on Java from Megen and Ammerzoden in Indonesia. After the Japanese occupation it moved to Pacet, also on Java, where the monastery still exists.
The sisters from Ammerzoden ended up in Hoogcruts in 1945 as a result of the Second World War, and a number of them lived in Kerkrade until 1957. The sisters from Hoogcruts founded a monastery in Hengelo in 1951. In 1960 they founded a monastery in Nieuwe Niedorp that existed until 1989. The sisters who remained behind moved to Silvolde in 1970, where the monastery was closed in 1981, after which most of the sisters, together with some from Megen and Nieuwe Niedorp, founded the Clarissen monastery "De Bron" in Nijmegen.
Meanwhile, in 1987, a number of sisters from Megen took the initiative to found the rest home "Het Witven" in Someren. Many Poor Clares, including those from other monasteries, eventually ended up here.