Jamison has said she is an "exuberant" person who longs for peace and tranquility but in the end prefers "tumultuousness coupled to iron discipline" to a "stunningly boring life." In An Unquiet Mind, she concluded:
I long ago abandoned the notion of a life without storms, or a world without dry and killing seasons. Life is too complicated, too constantly changing, to be anything but what it is. And I am, by nature, too mercurial to be anything but deeply wary of the grave unnaturalness involved in any attempt to exert too much control over essentially uncontrollable forces. There will always be propelling, disturbing elements, and they will be there until, as Lowell put it, the watch is taken from the wrist. It is, at the end of the day, the individual moments of restlessness, of bleakness, of strong persuasions and maddened enthusiasms, that inform one's life, change the nature and direction of one's work, and give final meaning and color to one's loves and friendships.
Jamison was born to Dr. Marshall Verdine Jamison (1916–2012), an officer in the Air Force, and Mary Dell Temple Jamison (1916–2007). Jamison's father, and many others in his family, had bipolar disorder.
As a result of Jamison's military background, she grew up in many different places, including Florida, Puerto Rico, California, Tokyo, and Washington, D.C.. She has two older siblings, a brother and a sister, who are three years and half a year older, respectively. Her niece is writer Leslie Jamison. Jamison's interest in science and medicine began at a young age and was fostered by her parents. She worked as a candy striper at the hospital on the Andrews Air Force Base .
Jamison moved to California during adolescence, and soon thereafter began to struggle with bipolar disorder. She continued to struggle in college at UCLA. At first she wanted to become a doctor, but because of her increasing manic episodes she decided she could not maintain the rigorous discipline needed for medical school. She then found her calling in psychology. She flourished in this field and was extremely interested in mood disorders. Despite her studies, Jamison did not realize she was bipolar until three months into her first job as a professor in UCLA's Department of Psychology. After her diagnosis, she was put on lithium (medication), a common drug used to contain moods. At times, she would refuse the medication because it impaired her motor skills, but after a greater depression she decided to continue to take it. Jamison once attempted suicide by overdosing on lithium during a severe depressive episode.
Jamison is an Episcopalian, and was married to her first husband, Alain André Moreau, an artist, during her graduate school years. She then married Dr. Richard Wyatt in 1994; they remained married until his death in 2002. Wyatt was a psychiatrist who studied schizophrenia at the National Institutes of Health. Their romance is detailed in her memoir Nothing Was the Same.
In 2010, Jamison married Thomas Traill, a cardiologist and colleague of hers at Johns Hopkins.