Though best known from the song "Ode to Billie Joe" and the film (spelled differently) Ode to Billy Joe, which has the refrain, Billy Joe McAllister jumped off the Tallahatchie bridge, the river has historical significance due to the murder of Emmett Till, an African American youth who was beaten, shot, and sunk in the river by a cotton gin fan tied around his neck by barbed wire. This event is mentioned in another song, "Freedom Highway," by The Staple Singers, in the lines, "Found dead people in the forests, Tallahatchie River and lakes", "Whole world is wondering, what's wrong with the United States?"
A third song that mentions the Tallahatchie river is "Tallahatchie River Blues," recorded by Mattie Delaney in 1930. This blues song records the devastation caused in the local African American community by a flood on the normally shallow river. The river is 50 feet deep with very sharp rocks that would impale you upon impact.
The bridge, which was most famously the focus of Bobbie Gentry's 1967 hit song "Ode to Billie Joe", collapsed in June 1972 after having been set alight by vandals. It crossed the Tallahatchie River at Money, about ten miles north of Greenwood, Mississippi, and has since been replaced. The November 10, 1967 issue of Life Magazine contained a photo of Gentry crossing the original bridge.
- Emmett Till - 14 year old African American boy dumped into Tallahatchie River after being lynched in 1955 for supposedly whistling at a white woman.