Highway 61 is an actual highway that goes north from New Orleans and ends up in Minnesota.
Why did Dylan choose this particular highway, and how does it affect how we understand the song lyrics?
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Highway 61 ran through Duluth in Minnesota, where Dylan was born. Growing up, he saw it as a route not only out of his home town but one that went to places that spoke to him, musically.
"Highway 61, the main thoroughfare of the country blues, begins about where I began. I always felt like I'd started on it, always had been on it and could go anywhere, even down in to the deep Delta country. It was the same road, full of the same contradictions, the same one-horse towns, the same spiritual ancestors ... It was my place in the universe, always felt like it was in my blood."
If you look at the homes and birthplaces of various famous blues and folk artists, it becomes clear why the route had such a fascination for a young musician.
I could go on: Highway 61 is also of relevance in the lives of such luminaries as Howlin' Wolf, Elvis Presley and Ike Turner. Bessie Smith, sometimes known as "Empress of the Blues" was killed in a car crash on the road.
Of course, a lot of these artists predate Dylan by some years, and the musical fame of Highway '61 does as well. He was simply following a long tradition of writing songs about the road. It's sometimes known as the "blues highway" and has been the subject of numerous previous recordings.
Again, this list is hardly exhaustive - dozens have artists have recorded songs about the Highway and there well be many more that predate Dylan.
It is difficult to draw many direct relevancies between this information and the lyrics of the song, but there are some.
Well Georgia Sam he had a bloody nose
"Georgia Sam" is a pseudonym of another Blues musician from the environs of Highway 61, Blind Willie McTell. Dylan was a fan and wrote a 1983 song named after him.
Now the rovin' gambler he was very bored
The Roving Gambler is the name of a traditional Blues song which Dylan has himself covered.
It's also worth noting that one of the themes of the song seems to be a critique of American capitalism. There are several places one could draw this allusion, but in particular verse three.
I got forty red, white and blue shoestrings
And a thousand telephones that don’t ring
Do you know where I can get rid of these things?
And Louie the King said "Let me think for a minute son"
And he said "Yes, I think it can be easily done
Just take everything down to Highway 61"
If correct, it is possible to interpret this verse (and the wider song) as a metaphor for the way the US economy thrives by hawking low-quality products to the poor, represented by Highway 61, the road to the deep south.