Lysacek, who won gold at the 2010 Olympics in Vancouver, told Matt Lauer on NBC's "Today" show "my road to Sochi ends here" because of a hip injury he sustained in September.
The 28-year-old skater said he tore a labrum, a ring of cartilage around his left hip, while preparing for the U.S. Championships scheduled for January. His last chance to quality for the event was the Ukraine open on Dec. 18.
Pain from the labrum injury had become "unmanageable," he said, despite aggressive treatment and physical therapy.
Lysacek said his doctor had warned him "that if I continued to train with 100 percent certainty the injury would get worse, the pain would get worse every single day and I could be doing permanent and severe damage."
The two-time U.S. champion had previously suffered a groin injury and a sports hernia.
"It's very difficult for me to say that, but my road to Sochi ends here,'' he told Lauer.
He added: "The last several weeks have been so painful for me that I don't want those to be my last moments on the ice after such a great career. I love to represent my country, and I'm determined to be healthy and skate again and really be the one that decides when it's over."
Lysacek was among the top three finalists in 20 out of 22 events at world championships, major international competitions and the Olympics between 2005 and 2010. In August 2012, he announced he intended to defend his title at the Winter Olympics in Sochi, Russia, the first U.S. male skater to attempt to do so since Dick Button in 1952.