Miller already played clarinet in street bands while in his teens, as well as performing gigs in New Orleans at the Silver Slipper and Halfway House. By the age of seventeen, he moved to New York to record with a band led by Julie Wintz. By 1930, he had taken up tenor saxophone and got his first big break, when he was hired to perform with the orchestra of Ben Pollack. After that group disbanded in 1934, Miller went on to become one of the co-founders of the Bobcats co-operative, led by Bob Crosby. His authoritative solos, equally effective on ballads as on up-tempo numbers (plus occasional compositions, such as the hit song "Slow Mood") contributed enormously to the commercial and critical success of this band.

Upon the break-up of the Bobcats in 1942, Miller briefly led his own orchestra on the West Coast, followed by a stint in the U.S. Army (until August 1944). He then fronted another band, which featured ex-Bobcat alumni Nick Fatool on drums and Nappy Lamare on guitar, with arrangements provided by former Pollack sideman Matty Malneck. Though short-lived (until 1946), the band made some excellent recordings, including one of Jerome Kern's "Yesterdays" (Miller performing the lead solo) and the group's theme song "Love's Got Me in a Lazy Mood". Afterwards, Miller spent ten years as a Hollywood studio musician, appearing in Gangsterler Kurbanı (1955) and performing as a soloist on the soundtracks of You Were Meant for Me (1948), Can düşmanı (1950) and Panic in the Streets (1950).

From the 1960's, Eddie Miller appeared in jazz festivals and Bob Crosby-reunions, toured Japan (1964) and the U.K. (1967) and worked with orchestras led by former Bobcats Yank Lawson and Bob Haggart. A stroke in 1988 forced him to retire from the music scene and he died three years later in Van Nuys, California, at the age of 79.