In spite of his wishes to continue his efforts to change society, Woody's own health began to decline. By 1949 Woody's behavior became increasingly erratic and he became more and more restless and unhappy as his friends, who thought he was behaving strangely, even for him, began to avoid him. Woody resumed his cross-country wanderings, and Marjorie, fearing for her children, now numbering three, told him in no uncertain terms that their marriage was over. While visiting friends on the west coast, Woody met Anneke Marshall. They lived briefly in Florida, then in a small apartment in New York City, where Anneke gave birth to their daughter Lorina Lynn in 1954. However, Woody was grasped in the ever-tightening clutches of what had been identified as Huntington's disease, the disease of his mother.

Woody would spend much of the rest of his life in Greystone Park Hospital in New Jersey, but even as he began writing increasingly more scattered songs such as Jesus My Doctor, his fame was spreading. The end of the McCarthey era and the folk revival of the 1960s made him well known. A pair of long-time fans, Sidsel and Bob Gleason, a couple who lived near the hospital began having week-end get-togethers centered around Woody. Friends, and fans, including Bob Dylan, came to sing and talk with Woody. Marjorie and the children visited as well.

After years of battling Huntington's disease, though surrounded by the support of his friends and admirers, Woody died on October 3, 1967.

However, his legacy lives on in his music, which inspired the folk revival of the 1960s, and continues to be heard today. In his hopes for change, we can find our own power to speak up and stand up.