Enlightenment thinkers were drawn to the new "science," formulated in the 17th century, which held that nature - including human nature - was uniform and subject to universal, unbending laws. The champion of the new science was the English scientist Isaac Newton. In his greatest work, the Principia Mathematica (1687), Newton applied fundamental mathematical principles to the study of physics. He established regular laws for such things as velocity, force, inertia, and acceleration. In the eyes of many thinkers, Newton's mathematical descriptions of physical regularities in the world represented the highest achievement of human thought to date. Newton portrayed a world of regularity, predictability, and order that revealed God's perfect design. The Principia was so convincing that many of its readers were inspired to seek law-like regularities for the social world as well. As the mysteries of nature had been revealed, so too would the mysteries of mankind. This is why the new science was so dear to the Enlightenment thinkers: it provided a methodology, dependent on reason, for investigating all aspects of the world around them.

The new science also contributed to deism, a religious development central to the Enlightenment spirit. The new faith in natural laws and scientific explanation eroded the belief in miracles. Science established the infinity of the universe, so that humans no longer seemed to be at the center of it. Many intellectuals - though far from all - began to develop a new theory of God. They rejected the idea of a personal God who had formed man in his own image and who constantly directed human affairs. Some Enlightenment thinkers rejected the divinity of Jesus Christ and the concept of the Trinity. For many Enlightenment thinkers, God was an impersonal deity who had set the universe in motion, but who had withdrawn from any further involvement in the world. God was, in their eyes, little more than the power of nature. Many deists described God as the "watchmaker" of a fully mechanical universe.

These theological conceptions clashed with traditional Christianity, and many enlightened thinkers tried to remake the Christian church from within by reducing it to a rational religion, stripped of its miraculous and supernatural elements. Enlightenment thinkers frequently blasted the political power and wealth of the clergy, and also judged the functionality of religion, that is, in terms of its usefulness, not its truth. The Enlightenment also produced new organizations that were akin to "New Age" religions. Groups such as the Free Masons and the Rosicrucians combined secretive fraternal sociability, esoteric lore, magic, and proto-political discussion. Although they were dedicated to reason and science, some radical Enlightenment thinkers nevertheless developed symbolic rites and ideological doctrines to use against orthodox Christianity.

The philosophes also directly attacked the institution of the Church. In a celebrated case, the French philosopher Voltaire (1694-1778) publicly defended the reputation of Jean Calas, a Protestant who had been executed on the dubious charge that he had murdered his son to prevent him from converting to Catholicism. When Voltaire propagated the phrase, "écrasez l'infâme" ("crush the infamy"), the "infamy" he wanted to crush was that of the Church's alleged bigotry, superstition, and intolerance. Such attacks achieved some success. Enlightened despots were eager to crush the independent power of the Church, and were more than happy to ally themselves with the anti-clerical philosophes. The Catholic Jesuits, who were very devoted to the authority of the Pope, were the most violently despised (even though many of the French philosophes had been educated by the Jesuits).

Enlightenment thinkers achieved a victory over the Jesuits when France, along with other countries, banned the Jesuits in the 1760s, and again when the Pope dissolved the order in 1773. The Jesuits were not reestablished until early in the 19th century.

The most radical of Enlightenment thinkers included materialists and atheists. The German Baron d'Holbach was one such atheist, as was the French scientist Laplace. Laplace claimed that, given the knowledge of every particle's position and movement in the universe, a person could (theoretically, at least) calculate every past and future condition of the universe. To Napoleon's query of what he thought of God, Laplace replied brashly, "I don't require that hypothesis." (Why was the Christian Church a target of the Enlightenment?)