Sheldrake's ideas have often met with a hostile reception from some scientists, including accusations that he is engaged in pseudoscience.

Sheldrake was born in Newark-on-Trent, Nottinghamshire to a family of Methodists. He attended Worksop College, an Anglican boarding school, and specialized in science. His father was an amateur naturalist and microscopist who encouraged his son's interest in plants and animals.

He obtained a scholarship to study Natural Sciences at Clare College, Cambridge. He specialized in biochemistry, graduated with double-first-class honours, and won the University Botany Prize. He was awarded a Frank Knox fellowship to study philosophy and history at Harvard University, at around the time Thomas Kuhn's The Structure of Scientific Revolutions (1962) was published, which he writes informed his view on the extent to which the mechanistic theory of life is just a paradigm. He returned to Cambridge, where he obtained his Ph.D. in biochemistry.

He became a Fellow at Clare College, director of studies in biochemistry and cell biology, and a Research Fellow of the Royal Society. From 1974 to 1985, he worked in Hyderabad, India, where he was Principal Plant Physiologist at the International Crops Research Institute for the Semi-Arid Tropics. For a year and a half he lived in the ashram of Bede Griffiths, where he wrote his first book, A New Science of Life.

As a biochemist, Sheldrake researched the role of auxin, a plant hormone, in the differentiation of a plant's vascular system. He ended this line of study when he concluded, "The system is circular, it does not explain how [differentiation is] established to start with. After nine years of intensive study, it became clear to me that biochemistry would not solve the problem of why things have the basic shape they do." More recently, drawing on the work of French philosopher Henri Bergson, Sheldrake has proposed that memory is inherent to all organically formed structures and systems. Where Bergson denied that personal memories and habits are stored in brain tissue, Sheldrake goes a step further by arguing that bodily forms and instincts, while expressed through genes, do not have their primary origin in them. Instead, his hypothesis states, the organism develops under the influence of previous similar organisms, by a mechanism he has dubbed morphic resonance.

In September 2005, Sheldrake received the Perrott-Warrick Scholarship for psychical research and parapsychology, which is administered by Trinity College, Cambridge. As a result, he is the current Director of the Perrot-Warrick Project.

Rupert Sheldrake is presently the Academic Director for the Holistic Thinking program at The Graduate Institute Bethany

In April 2008, Sheldrake was stabbed in the leg during a lecture at the La Fonda Hotel in Santa Fe, New Mexico. He was presenting as part of the tenth annual International Conference on Science and Consciousness. Sheldrake has since recovered. The assailant, Japanese born laborer Kazuki Hirano, allegedly stabbed Sheldrake because he believed that Sheldrake was using mind control techniques on him. He had followed Sheldrake to New Mexico from England to purportedly ask him how to block mental telepathy when he stabbed him. Sheldrake fears that if he is released and extradited to Japan, he will continue to stalk him.

Sheldrake has a Methodist background but after a spell as an atheist found himself being drawn back to Christianity when in India, and is now an Anglican.

Sheldrake has made appearances in popular media, both on radio and on television. He was the subject of a one of a six-part documentary series called "Heretic", broadcast on BBC 2 in 1994. On May 18, 2009, he appeared on The Museum of Curiosity on BBC Radio 4.