Educated in Latin and Aristotelian physics at the University of Oxford, Wren was a notable astronomer, geometer, mathematician-physicist as well as an architect. He was a founder of the Royal Society (president 1680–82), and his scientific work was highly regarded by Sir Isaac Newton and Blaise Pascal.

Wren was born at East Knoyle in Wiltshire, the only surviving son of Christopher Wren DD (1589–1658), at that time the rector of East Knoyle and later Dean of Windsor. A previous child of Dr Wren, also named Christopher, was born on 22 November 1631, and had died the same day. John Aubrey’s confusion of the two persisted occasionally into late twentieth-century literature.

As a child Wren "seem'd consumptive". Although a sickly child, he would survive into robust old age. He was first taught at home by a private tutor and his father. After his father's appointment as Dean of Windsor in March 1635, his family spent part of each year there. Little is known about Wren’s life at Windsor.

Little also is known of Wren’s schooling. The story that he was at Westminster School from 1641 to 1646 is unsubstantiated. Parentalia, the biography compiled by his son, a third Christopher, places him there "for some short time" before going to Oxford (in 1650). Some of his youthful exercises preserved or recorded (though few are datable) showed that he received a thorough grounding in Latin; he also learned to draw. According to Parentalia, he was "initiated" in the principles of mathematics by Dr William Holder, who married Wren’s elder sister Susan (or Susanna) in 1643. During this time period, Wren manifested an interest in the design and construction of mechanical instruments. It was probably through Holder that Wren met Sir Charles Scarburgh whom Wren assisted in his anatomical studies.

On 25 June 1650, Wren entered Wadham College, Oxford where he studied Latin and the works of Aristotle. It is anachronistic to imagine that he received scientific training in the modern sense. However, Wren became closely associated with John Wilkins, who served as warden in Wadham. Wilkins was a member of a group of distinguished scholars. This group, whose activities led to the formation of the Royal Society, consisted of a number of distinguished mathematicians, original and sometimes brilliant practical workers and experimental philosophers. This connection probably influenced Wren’s studies of science and mathematics at college. He graduated B.A. in 1651, and three years later received M.A.

Receiving his M.A. in 1653, Wren was elected a fellow of All Souls College in the same year and began an active period of research and experiment in Oxford. His days as a fellow of All Souls ended when Wren was appointed Professor of Astronomy at Gresham College, London in 1657. He was provided with a set of rooms and a stipend and was required to give weekly lectures in both Latin and English to all who wished to attend; admission was free. Wren took up this new work with enthusiasm. He continued to meet the men with whom he had frequent discussions in Oxford. They attended his London lectures and in 1660, initiated formal weekly meetings. It was from these meetings that the Royal Society, England’s premier scientific body, was to develop. He undoubtedly played a major role in the early life of what would become the Royal Society; his great breadth of expertise in so many different subjects helping in the exchange of ideas between the various scientists. In fact, the report on one of these meetings reads:

In 1662, they proposed a society "for the promotion of Physico-Mathematicall Experimental Learning." This body received its Royal Charter from Charles II and "The Royal Society of London for the Promotion of Natural Knowledge" was formed. In addition to being a founder member of the Society, Wren was president of the Royal Society from 1680 to 1682.

In 1661, Wren was elected Savilian Professor of Astronomy at Oxford, and in 1669 he was appointed Surveyor of Works to Charles II. From 1661 until 1668 Wren's life was based in Oxford, although the Royal Society meant that he had to make occasional trips to London.

The main sources for Wren's scientific achievements are the records of the Royal Society. His scientific works ranged from astronomy, optics, the problem of finding longitude at sea, cosmology, mechanics, microscopy, surveying, medicine and meteorology. He observed, measured, dissected, built models, and employed, invented and improved a variety of instruments. It was also around these times that his attention turned to architecture.

It was probably around this time that Wren was drawn into redesigning a battered St Paul's Cathedral. Making a trip to Paris in 1665, Wren studied the architecture, which had reached a climax of creativity, and perused the drawings of Bernini, the great Italian sculptor and architect. Returning from Paris, he made his first design for St Paul’s. A week later, however, the Great Fire destroyed two-thirds of the city. Wren submitted his plans for rebuilding the city to King Charles II, although they were never adopted. With his appointment as King’s Surveyor of Works in 1669, he had a presence in the general process of rebuilding the city, but was not directly involved with the rebuilding of houses or companies' halls. Wren was personally responsible for the rebuilding of 51 churches; however, it is not necessarily true to say that each of them represented his own fully developed design.