Many of Chopra’s themes and beliefs are stated in his first book Creating Health, in 1986. He launched himself as a staunch advocate of the connection between mind and body, advocating meditation and self-awareness as primary factors in both illness and healing. He deepened these themes in Quantum Healing (1989), where he examined the mysterious phenomenon of spontaneous healing of cancer. In addition to the spontaneous healing of cancer, Chopra in his 2001 book Grow Younger, Live Longer makes reference to a "friend of ours who was diagnosed with AIDS fifteen years ago" made a miraculous turn around and now has undetectable level of the HIV antibodies in his blood. Here he introduced quantum physics as a means of understanding the mind-body connection, arguing—as he would in many other books—that consciousness is the basic foundation of nature and the universe.In his book Life After Death: The Burden of Proof (2006), he extends personal consciousness beyond the "artificial boundary that separates the living from the departed." Assessing the seven varieties of the afterlife described by various world religious traditions, Chopra offered the proposal that a person’s awareness in the present shapes existence after death; that is, the afterlife is created uniquely for each of us by our present level of consciousness.

Chopra taught at Tufts University and Boston University Schools of Medicine, and became the Chief of Staff at the New England Memorial Hospital (later the Boston Regional Medical Center) in Stoneham, Massachusetts. Chopra also established a large private practice. Chopra is the co-founder of the Chopra Center, which he founded in 1996 in La Jolla, California with Dr. David Simon. In 2002, the Center moved its official headquarters to La Costa Resort & Spa in Carlsbad, California with a branch in New York City. He has plans for other centers. In 2004, Chopra was recruited to co-write a script with Indian film director Shekhar Kapur on a proposed film to be made about the life of Siddhartha Gautama, the Buddha, but the plans were later dropped for unstated reasons.

Subsequent books have turned toward larger spiritual questions. In How to Know God (2000) and The Book of Secrets (2004), an argument is made for an all-pervasive intelligence that unites every living thing, rather than the traditional Western concept of God as a person, "a venerable white male sitting on a throne in the sky." Chopra sees God as a projection of human awareness, who becomes more expansive and universal as individual consciousness expands.

Chopra has been both lauded and criticized for his frequent references to the relationship of quantum mechanics to healing processes, a connection that has drawn skepticism from physicists who say it can be considered as possibly contributing to the general confusion in the popular press regarding quantum measurement, decoherence and the Heisenberg uncertainty principle.[20] In 1998, Chopra was awarded the satirical Ig Nobel Prize in physics for "his unique interpretation of quantum physics as it applies to life, liberty, and the pursuit of economic happiness". 

In 2005, Chopra became a staunch advocate for disarmament and international peace in Peace Is the Way, where he argues that a "critical mass" of people of like mind can defeat the global "addiction to war." In the same regard, he became president of a broad-based organization, Alliance of a New Humanity, that seeks to form "peace cells" around the world and to foster such related goals as environmental healing and sustainable economies in developing nations.In August 2005, Chopra posted a series of articles in the blog The Huffington Post, to which he is a frequent contributor, offering his solution to the creation-evolution controversy. In doing so he expressed support for Intelligent design without the Bible, or the politics of religion. According to Chopra, Nature itself displays intelligence.

In its May 22/29, 1991 issue, the Journal of the American Medical Association (JAMA) published an article coauthored by Chopra: Letter from New Delhi: Maharishi Ayur-Veda: Modern Insights Into Ancient Medicine. This article was represented as discussing traditional Indian medicine (Ayurveda). Upon investigation, JAMA editors found that the coauthors had financial interests in "Maharishi Vedic Medicine" products and services. In the 14 August 1991 edition of JAMA, the editors published a financial disclosure correction and followed up in October 2, 1991 with a six-page Medical News and Perspectives exposé. The series of events was reviewed by Skolnick in the Newsletter of the National Association of Science Writers. In response to the JAMA exposé, two Transcendental Meditation groups and Chopra sued the author, Andrew Skolnick, JAMA’s editor Dr. George Lundberg, and the AMA for $194 million in July 1992. Pursuant to a settlement agreement in 1993, the suit was dismissed by the judge at the request of the plaintiffs, with the option of reinstating pending completion of the settlement.

In 2008, following the November attacks in Mumbai, Chopra commented on the Larry King Live show that there is a wider historic context of terrorism. Solving terrorism is not simply a matter of killing the terrorists involved. He spoke of how that larger context of terrorism included the role of the US military policies in Pakistan and Afghanistan over the past thirty years. These policies include the Bush Administration’s War on Terror. Chopra also speculated that Muslim extremists were threatened by the election of US president Barack Obama. In danger of losing their primary ideological recruiting tool with the loss of a right wing administration, the terrorists may have staged their attack now in order to elicit a response that would garner maximum sympathy on the Muslim street.