After getting married in 1937, he moved to Los Angeles and formed a trio. In 1939 he began to sing to provide some variety to the band's music. The trio was hired as the house band for the 331 Club in 1942 and a year later—when he was just 25 years old—they got their first real big break with the song Straighten Up and Fly Right, which described a monkey on a buzzard's back. The song signaled the expansion of Cole's music into pop and his popularity increased. His solo career began to take off in the early 1950s. By 1955 the trio broke up, since the role of the other members became just his backup.
The next milestones came in 1956. Cole participated in the first mixed-race performance in Birmingham, Alabama. An group angry white members of the audience stormed the stage and beat Cole and the other performers. To the chagrin of many African Americans, Cole forgave them, but eventually he was recognized for his composure and dignity in handling the situation. Cole did support the Civil Rights movement. For example, he sued hotels in Illinois and Pennsylvania for not allowing himself and other African Americans to stay in them. Also that same year, Cole became the first African American to host a variety tv show (despite being well received, it only lasted 30 episodes because there was no national sponsor, a fact Cole blamed on the fact that he was a black man).
His presence on the pop charts slowed down in the late 1950s but he still remained a popular artist. In 1964, years of smoking caught up to him, and he died a few months after learning he had lung cancer. He was only 45 years old when he passed away. His funeral was attended by Frank Sinatra, Rosemary Clooney, and other celebrities of the day.