The non-adherence to the notion of an omnipotent creator deity or a prime mover is seen by many as a key distinction between Buddhism and other religions. Rather, Buddhism emphasizes the system of causal relationships underlying the universe (pratitya samutpada) which constitute the natural order (dharma). No dependence of phenomena on a supernatural reality is asserted in order to explain the behaviour of matter. According to the doctrine of the Buddha a human being must study Nature (dhamma vicaya) in order to attain personal wisdom (prajna) regarding the nature of things (dharma). In Buddhism the sole aim of spiritual practice is the complete alleviation of stress in samsara, called nirvana. The Buddha explicitly rejects a creator, denies endorsing any views on creation and states that questions on the origin of the world are worthless.

Some teachers tell students beginning Buddhist meditation that the notion of divinity is not incompatible with Buddhism,, and at least one Buddhist scholar has indicated that describing Buddhism as 'non-theistic' may be overly simplistic; but many traditional theist beliefs are considered to pose a hindrance to the attainment of nirvana, the highest goal of Buddhist practice. Despite this apparent non-theism, Buddhists consider veneration of the Noble ones very important, although the two main traditions of Buddhism differ mildly in their reverential attitudes. While Theravada Buddhists view the Buddha as a human being who attained nirvana or Buddhahood, through human efforts, some Mahayana Buddhists consider him an embodiment of the cosmic Dharmakaya, born for the benefit of others. In addition, some Mahayana Buddhists worship their chief Bodhisattva, Avalokiteshvara, and hope to embody him.