She is of mixed ancestry: her father is half-Chinese and half-Welsh, while her mother is half-Chinese, quarter-Iranian, and quarter-German. Mok attended Diocesan Girls' School from primary to secondary grade in Hong Kong. When she was a F.5 student, she received the 1st Hong Kong Outstanding Students Awards. She later left Hong Kong in 1987 and studied abroad. She attended United World College of the Adriatic near Trieste, Italy from 1987 to 1989, and majored in Italian literature when studying at Royal Holloway, University of London.
In her initial Hollywood productions such as Around the World in 80 Days (2004) Mok used her birth name Karen Joy Morris, but went to using her stage name Karen Mok for all Future productions such as Man of Tai Chi (2013) . She also supplied the voice of Princess Kida for the Cantonese dub of Walt Disney's Atlantis: The Lost Empire (2001). Mok played the female lead in the 10th anniversary Asian tour of the hit Broadway musical Rent in the lead role of Mimi in 2005 and 2006.
In 2007, Mok was involved with MTV EXIT, a campaign against human trafficking in Asia. She presented Traffic: An MTV EXIT Special, a documentary on trafficking. Karen currently serves as ambassador for UNICEF, SPCA, Animals Asia Foundation, Enlighten-Action for Epilepsy, Care for Children, and Roll Back Malaria (RBM).
Mok carried the torch at the 2008 Summer Olympics held in Beijing and performed at the opening and closing ceremonies. In October 2008, she launched her own brand of perfume in Hong Kong.
Mok married her first boyfriend, German-born Johannes Natterer, at a church near Florence, Italy, on 1 October 2011. Mok has 3 step-children and spends her time between London and her international engagements.