She was born in Cleveland, Ohio the third child of Loren Prentiss and Ellen Rebecca Rouse.
She graduated from Miss Fisher's School for Girls in 1886. She then attended Vassar College where she graduated Phi Beta Kappa with degree in music in 1890. At Vassar, Hughes performed in and planned tours for the college's glee club.
Hughes was interested in teaching and considered pursuing a Ph.D. Ellen feared that too much education would turn Hughes into a bluestocking so she insisted Hughes travel through Europe rather than further her education.
Upon returning to Cleveland in the early-1890s, Adella played piano as a soloist and accompanist, and organized concerts. After the failure of a local Cleveland symphony orchestra, Hughes organized a Cleveland Symphony Concert Series in 1901. The series began with a concert by the Pittsburgh Symphony. Soon, she was one of Cleveland's major impresarios, regularly engaging orchestras to perform at Grays Armory. She supplied the city with a series of musical attractions, including orchestras, opera, ballet, and chamber music.
The financial success of Hughes's concert series came from her decision to have individual investors fund each concert and receive repayment from the concert's profits. In 1915, Hughes created the Musical Arts Association, and three years later she formed the Cleveland Orchestra and was its first general manager. That same year, she invited Nikolai Sokoloff to join the Musical Arts Association and lead the Cleveland Orchestra.
Under her leadership, the Cleveland Orchestra rose to national prominence, touring the country and recording their performances. Victor Herbert, conductor of the Pittsburgh Symphony, said that Hughes knew “more about the business of music than anyone,” and that he “would rather have her for... manager than any man in the world."
Hughes served as a manager of this orchestra for 15 years, and as administrator of the Musical Arts Association for thirty years. She also helped found the Cleveland Music School Settlement.
She married Felix Hughes, a professional singer, in 1903. The couple divorced in 1923.
Hughes died on August 23, 1950 in Cleveland, Ohio. She is buried in Cleveland's Lake View Cemetery.