Harris had been determined to feature in the Ashes, having spent the past six months on a carefully managed program in an effort to be fully fit for the tour.
Even last week, the right-armer declared his intent to play all five Tests.
But after being sent for two rounds of scans in London this week, it became clear on Friday he would take no part in the series.
"Given the news I received yesterday, and after talking it over with my family, I know now is the right time to step away from cricket," Harris said.
"I'm pretty lucky, I have had a wonderful career and nothing made me prouder than pulling on the baggy green.
"I played 27 more Tests than I ever thought I would and I have relished every single moment.
"I couldn't have played with a better bunch of blokes and walking away from the team and our support staff is probably the hardest thing to stomach."
It ends a short but sterling career - Harris suffered major achilles, knee, hamstring and hip injuries but snared 113 wickets at an average of 23.52.
Often restricted by his degenerative knee, Harris was renowned for putting pain to one side on the pitch.
It was a trait best exhibited in Cape Town last year, when he bowled Australia to a Test series victory with 27 balls to spare despite being unable to lift his leg before play.
Long-stalled major knee surgery followed.
"Ryan always gave it his all for his country and he epitomises everything the baggy green stands for," coach Darren Lehmann said.
"I was lucky enough to captain Ryan as a grade cricketer, a rookie player and as a state cricketer. He was one of the most-talented players I had ever seen.
"His never-say-die attitude was his signature as he left absolutely nothing on the field each time."
Harris, who has previously spoken of his desire to coach, will stay with the squad in England.
"Whatever is next for me, and I don't know what that is right now, I know it will still involve cricket," he said.
"That is what I love and I want to be able to give back to the game that has given me so much."
- AAP
