Judge Melvyn Bragg called the story, which is set in Detroit in the early 20th century, "an outstanding work of fiction".
The writer beat five other authors to the title, including Man Booker Prize winner Hilary Mantel.
The winner was announced at an awards dinner in Oxford.
"I've read this story many times and still find it profoundly moving," Bragg said.
Roshi Fernando, Yiyun Li, Will Cohu, Gerard Woodward and Mantel will all receive £500 for making the shortlist.
This is the second time in as many months that Doerr has been awarded a prize for fiction.
He recently won The Story Prize in the USA, for Memory Wall, his second collection of short stories.
The Sunday Times Short Story Award was launched last year to honour the success of short-fiction writers.
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