Born and raised in Ireland, she worked as a model before marrying Galen Weston in 1966. They moved to Toronto in 1974, and Weston became a Canadian citizen. They have two married children, Alannah and Galen, Jr., one granddaughter and one grandson.

Prior to her appointment as Lieutenant Governor, Weston spent over two decades working in business and in the fashion industry. As deputy chair of Holt Renfrew, she promoted Canadian design and merchandise. During the same time, she also served as director of Brown Thomas & Co. in Ireland, co-founded Torwest in the United States, and served as vice-chair and design director of the Windsor Club in Florida.

In 1979, Weston founded the Ireland Fund of Canada, a non-partisan, non-denominational organization that funds community projects in Ireland to promote peace. She continues to serve as an honorary patron of the organization.

An interest in early childhood education led Weston to serve as founding chair of the Mabin School in Toronto. She also co-founded and chaired the Canadian Environment Educational Foundation, and established the Winter Garden Show at the Royal Agricultural Winter Fair. Weston has explored her longstanding interest in homes and gardens as co-author of two best-selling books, In a Canadian Garden (1989) and At Home in Canada (1995).

Since her retirement as Lietenant Governor, Mrs. Weston has spearheaded the most successful fundraising campaign in Canadian cultural history, which raised more than $250 million for the Royal Ontario Museum. She is patron of several organizations dealing with social issues, such as the Abbeyfield House Society, the Hospice Association of Ontario, the Landmine Survivors Network, the Ontario March of Dimes and the Yonge Street Mission. Weston also devotes a significant proportion of her time, as well as her business and fashion expertise, to Selfridges, the London department store of which she is a director.

Weston served as the first chancellor of the Order of Ontario, and received the honour in 2001. She was appointed a Member of the Order of Canada in 2003. She was invested as Dame of Justice in the Venerable Order of St. John in 1997, and received the Queen's 2002 Golden Jubilee Medal.

Ten post-secondary institutions have recognized Weston with honorary degrees, including the University of Western Ontario, University of St. Michael's College, University of Toronto, Massey College, Trinity College, Dublin and University College Dublin

Weston is the recipient of the 2009 YWCA Toronto Woman of Distinction President’s Award, for modeling leadership in public and private life.