Ramona had no acting training prior to her role on Outnumbered (2007), making her exactly what the producers were looking for. When Ramona was five, she was spotted by the script writer's wife at a birthday party and was immediately recommended for the role of "Karen" because of her "Interesting personality" and ability to be "sure of herself without being precocious". Ramona took on the role of "Karen Brockman" and, in 2007, five-year-old Ramona captured the hearts of people all over Britain with her quick wit and childish charm. Ramona can still be seen as "Karen" on the BBC1 today, three years after her debut.

In 2009, Ramona booked the role of "Imogen Pollock" in the made-for-TV Movie Enid (2009), detailing the life of children's writer Enid Blyton.

Later in 2009, Ramona became the first child to win the British Comedy Award for "Best Female Comedy Newcomer". Outnumbered (2007) also won two other comedy awards on the night, including "Best TV Comedy".

Ramona Marquez's father, Martin Marquez, and uncle, John Marquez, are both actors.