Charles was 16 when his father, Benedict Leonard Calvert, 4th Baron Baltimore died, passing on his title. Shortly after his father's death, the title to Maryland was restored to the Calvert family who had lost it following the Glorious Revolution.
In 1732, under Governor Samuel Ogle, Maryland was engaged in a border dispute with Pennsylvania. Several settlers were taken prisoners on both sides and Penn sent a committee to Governor Ogle to resolve the situation. Rioting broke out in the disputed territory and Ogle appealed to the King for resolution.
Faced with this situation, Charles arrived in Maryland and assumed charge of the colony in 1732. Charles unwittingly agreed to a settlement based on an inaccurate map causing him to renege on the agreement. Charles's error ultimately resulted in the loss to the territory of approximately one thousand square miles.
On July 20 1730 Charles married Mary Janson, the daughter of Theodore Janson and Williamza Henley. Charles and Mary had three children: Frederick Calvert who succeeded his father to become the 6th and final Lord Baltimore, Louisa Calvert, and Caroline Calvert (who married Robert Eden). Charles was also survived by an illegitimate son, Benedict Swingate Calvert who married Elizabeth, daughter of Maryland Governor Captain Charles Calvert Butler and his wife Rebecca Gerard and granddaughter of Charles Calvert, 3rd Baron Baltimore. Benedict Swingate Calvert was the father of Eleanor Calvert the wife of John Parke Custis; they were the parents of George Washington Parke Custis and Eleanor Parke Custis Lewis. Eleanor Parke Custis married Lawrence Lewis, a son of Fielding Lewis and Betty Washington, a sister of George Washington; George Washington was the stepfather of John Parke Custis.
The home in which Charles Calvert resided at in Maryland still stands today.