Maria Caserini began acting in stage productions at an early age. Her first film was in 1906 for Cines in Rome, in what is considered the first film adaptation of Shakespeare's Othello, directed by Mario Caserini, her husband. She starred in Romeo and Juliet in 1908 and then in thirteen other films until 1909. One of these films was Macbeth, directed by her husband.

From 1910 to 1927 she acted in 65 films, many of them always directed by her husband, such as Lucrezia Borgia, whose performance gave her greater notoriety. She resumed theatrical activity soon after abandoning her film career.

She was buried in the Maggiore Cemetery in Milan, where her remains were later interred in a small cell.