[10] The 2012 biography Bruce by Peter Ames Carlin includes an interview with Springsteen's sister Ginny, in which she plainly states that the song is a precise description of her early life with her husband Mickey, to whom she is still married.

The imagery of the chorus and the end of the song were inspired by lines from Hank Williams' 1950 hit "Long Gone Lonesome Blues".

[13] The song's depiction of how economic difficulties are interlaced with local culture also presaged the 1980s popularity of heartland rock: I come from down in the valley, Where mister when you're young – They bring you up to do, like your daddy done

[16] Springsteen himself has noted that "Wreck on the Highway" is one of the songs reflecting a shift in his songwriting style, linking The River to Nebraska.

[21] The song was first performed in public at the Musicians United for Safe Energy concerts at Madison Square Garden in September 1979, and was featured in the subsequent 1980 film No Nukes three months before The River's release.

On later tours, especially in Europe, the song's outro was extended to great length, with audiences mass singing the wordless "oooh" parts at the end.

On the 1999–2000 Reunion Tour, "The River" was cast in a different arrangement that featured a Clarence Clemons saxophone part; one such rendition was included on the subsequent Live in New York City album and DVD.