In 1935 he can be found working at Jim Bell's Harlem club as a dancer, drummer and compare. About now he begins singing.
Following a booking at the Rhumboogie club in Chicago he is hired by bandleader Lucky Millinder.
He makes his recording debut with the Millinder orchestra on 26 May 1944, singing 'Hurry Hurry' and 'Who Threw the Whiskey in the Well'.
He appears for the first time at the Apollo Theater, Harlem.
'Who Threw the Whiskey in the Well' enters the Billboard chart in June. It will spend 20 weeks there and reach the Number 1 spot. Leaving Millinder, Wynonie records for the Philo and Apollo labels in Los Angeles, where he has been living since 1940.
The following year 'Wynonie Blues' and 'Playful Baby' (both on Apollo) chart briefly. Further recordings come out on Hamp-Tone and Bullet. Wynonie signs with the powerful Harold F. Oxley and Aladdin Records. In November 1946 he moves to New York.
After a couple of sessions for Aladdin, Wynonie signs with King Records and makes his first sides for the label on 13 December 1947. At the end of the year he cuts 'Good Rockin' Tonight' and as he enters the new year the song is Wynonie's second R&B Number 1. It is in the charts for six months
'All She Wants to Do is Rock' gives Wynonie his third (and as it turns out, last) Number 1 record. 'Grandma Plays the Numbers', 'I Feel That Old Age Coming On', 'Drinkin' Wine Spo-Dee-O-Dee' and 'I Want My Fanny Brown' also show up in the R&B Top 10. Wynonie buys a house in the Addisleigh Park district of St. Albans, a well-off black suburb.
In 1950 Wynonie begins going out on R&B package tours, playing one-nighters across the country. This summer's tour has him sharing the bill with Stick McGhee and Annie Laurie. He has four more R&B chart entries, the most successful, 'Sittin' on It All the Time', rising to Number 3.
The Harris-McGhee-Laurie package plays the Apollo Theater and goes on the road again. In July 1951, Wynonie stars in two big R&B in Los Angeles: the Cavalcade of Jazz and the Blues Jubilee. Then he goes on tour with T-Bone Walker and Lowell Fulson, later joined by Big Joe Turner.
His sole hit of the year is 'Bloodshot Eyes', which gets to Number 6.
'Lovin' Machine' is Wynonie's last chart record in 1952. He tours with the young pop-blues singer Larry Darnell. Among their bookings are a week at the Apollo and a one-nighter in Wynonie's home town Omaha.
Wynonie takes part in an extensive package tour in 1953, with Ruth Brown, Buddy Johnson, the Clovers, Lester Young, comedian Dusty Fletcher and boxer Joe Louis.
He records the Leiber-Stoller song 'Destination Love' for the Atco label but it goes nowhere. His career is in rapid decline, and he is forced to move out of Addisleigh Park house in 1956. He earns a living through managing bars.
After a three year absence from the recording studio, in 1960 he cuts some sides for Roulette, including a remake of 'Bloodshot Eyes', but only one single is released.
Wynonie is now living in Los Angeles. In August 1964 he makes his final recording in Chicago, three songs for Chess Records. The label does not issue them until after his death.
He is diagnosed as suffering from cancer of the throat, and on 14 June 1969 Wynonie Harris dies in the USC Medical Center in L.A.