Margaret was married to Suffolk's son, John de la Pole. The wedding may have been held between 28 January and 7 February 1444, when she was perhaps a year old, but certainly no more than three. However there is more evidence to suggest they were married in January or February 1450 after Suffolk had been arrested and was looking to secure his son's future.
Papal dispensation was granted on 18 August 1450 because the spouses were too closely related and this concurs with the later date of marriage.
Three years later, the marriage was dissolved and King Henry VI granted Margaret's wardship to his own half-brothers, Jasper and Edmund Tudor. Margaret never recognised this marriage. In her will, made in 1472, Margaret refers to Edmund Tudor as her first husband. Under canon law, Margaret was not bound by the marriage contract as she was entered into the marriage before reaching the age of twelve.