Knotts was married three times. His marriage to Kathryn Metz lasted from 1947 until their divorce in 1964, and he raised his daughter as a single parent.  He married Loralee Czuchna in 1974 and they divorced in 1983. His third marriage was to Frances Yarborough, from 2002 until his death in 2006. From his first marriage, Knotts had a son, Thomas Knotts, and a daughter, actress Karen Knotts (born April 2, 1954).

Knotts died at age 81 on February 24, 2006, at the Cedars-Sinai Medical Center in Los Angeles from pulmonary and respiratory complications of pneumonia related to lung cancer. CLR