The daughter of Thomas, Lord Berkeley, enraged at the thought that her inheritance (Berkeley Castle) must go to her nephew, instead, sued for possession, and started a family contest that lasted two centuries. At times courtroom hostilities burst into violent confrontations and in 1470 into a pitched battle at Nibley Green, in what is thought to be the last private battle in Britain.

The most famous event to take place in the castle was the gruesome murder of Edward Il. Edward, forced to abdicate at Kenilworth Castle by Earl Mortimer and Queen IsabelIa, (Edward's "She Wolf" wife) was imprisoned in Berkeley in May 1327. Attempts were made to make his death look "natural" by throwing animal carcasses into his cell in the hope that the vapors would either infect or asphyxiate him. However, Edward survived all this until his jailers, Sir John Maltravers and Sir Thomas Gurney, murdered him in September 1327 "with a hoote brooch (red-hot poker) putte thro the secret place posterialle". After his murder, it was officially announced that Edward of Caernarvon had died of natural causes.

In 1649, Cromwell's Civil War parliamentary troops attacked Berkeley Castle, which surrendered after a three-day siege, destroying some 35 feet of the west castle wall. The Berkeley family is still forbidden by law to repair the breach.

The Berkeley family was also prominent in American history producing two colonial governors, inventing Bourbon whiskey and donating a library at the University of California at Berkeley.