Carol Ann Susi had played the role of Mrs Wolowitz since 2007
Carol Ann Susi died in Los Angeles on Tuesday from cancer at the age of 62.
Stars of the show have paid tribute to Susi, calling her a "beloved" member of the cast.
Kunal Nayyar, who plays Howard's best friend Raj, said his heart was broken. "I will miss your smile. Your spirit is forever with us."
Melissa Rauch, who plays her daughter-in-law Bernadette on the show, tweeted: "So grateful to have known Carol Ann Susi who brought laughter and light with her always. She'll forever be in my heart."
Actress Mayim Bialik, who plays Amy Farrah Fowler, tweeted: "Beloved Carol Ann Susi passed away, yes. The voice of Mrs Wolowitz. Oh Carol Ann."
Warner Bros and producers of the hit comedy said in a
statement: "Unseen by viewers, the Mrs Wolowitz character became a bit
of a mystery throughout the show's eight seasons.
"What was not a mystery, however, was Carol Ann's immense
talent and comedic timing, which were on display during each
unforgettable appearance.
"In addition to her talent, Carol Ann was a constant source of joy and kindness to all."
Mrs Wolowitz's loud Brooklyn accent became a distinctive presence on the award-winning show.
Character actress Susi started her career in the 1970s and
made guest appearances on many well known shows including Seinfeld,
Married with Children, Ugly Betty and Greys Anatomy.
Howard Wolowitz (left) is one of a group of scientist friends on the CBS sitcom