Werburgh was born at Stone (now in Staffordshire), and was the daughter of King Wulfhere of Mercia (himself the Christian son of the pagan King Penda of Mercia) and his wife St Ermenilda, herself daughter of the King of Kent. She obtained her father's consent to enter the Abbey of Ely, which had been founded by her great aunt Etheldreda (or Audrey), the first Abbess of Ely and former queen of Northumbria, whose fame was widespread. Werburgh was trained at home by St. Chad (afterwards Bishop of Lichfield), and by her mother; and in the cloister by her aunt and grandmother. Werburgh was a nun for most of her life. During some of her life she was resident in Weedon Bec, Northamptonshire.
Werburgh was instrumental in convent reform across England. She eventually succeeded her mother Ermenilda, her grandmother Seaxburh, and great-aunt Etheldreda as fourth Abbess of Ely. She died on 3 February 700 and was buried at Hanbury in Staffordshire.
Following Werburgh's death, her brother Coenred became king of Mercia. In 708 he decided to move his sister's remains to a more conspicuous place within the church at Hanbury. When the tomb was opened, her body was found to be miraculously intact. This preservation was taken as a sign of divine favour. A year later Coenred had abdicated as king and taken holy orders, becoming a monk in Rome. It was at this time that the most famous story about Werburgh appeared, according to which she restored a dead goose to life, as recounted by the medieval hagiographer Goscelin. A stained glass window in the Church of St Peter and St Paul, Weedon Bec, Northamptonshire relates to another tale in which she was said to have banished all the geese from the village.
The shrine of St Werberh remained at Hanbury until the threat from Danish Viking raids in the late 9th century prompted their relocation to within the walled city of Chester. A shrine to St Werberh was established at the Church of St. Peter and St. Paul (the site is now occupied by Chester Cathedral). In 975, the Church of St. Peter and St. Paul was re-dedicated to St. Werburgh and the Northumbrian saint Oswald. A monastery in the names of these two saints was attached to the church in the 11th century.
By 1057 the Abbey church was rebuilt and further endowed by Leofric, Earl of Mercia. By this time, St. Werburgh was regarded as the patron saint and protector of Chester. A miracle attributed to her was the unexpected withdrawal of the Welsh king Gruffudd ap Llywelyn from besieging the city.