There is some evidence that all of the early great civilizations of the world - from the ancient Mesopotamians to the Egyptians, Greeks and Romans - have been strongly biased towards the right hand. The right hand of the gods was considered to be healing and beneficent, while their left hand was used for curses or inflicting injury. The strongly anti-left Ancient Egyptians often depicted their enemies as left-handed while they were the righteous dextrals.

In almost all of these cultures, the right hand was used for ceremonies and for eating, and the right-hand side was always the favoured position. An interesting example of just how deep this bias went can be seen in an Assyrian decorative bas-relief sculpture, in which two spirit figures appear to be almost completely symmetrical mirror images, except that, on closer inspection, it becomes clear that both figures are using their right hands to perform the ritual.

All the Abrahamic religions (Judaism, Christianity and Islam) developed out of strongly right-handed cultures in the Middle East, as can be seen in more detail in the section on Handedness and Religion.

The Ancient Greeks, even such intelligent and rational men as Plato and Aristotle, almost always associated the right with good and the left with evil and criminality. The great philosopher Plato was convinced that the limbs are naturally of equal strength and ability, and that any handedness is culturally imparted. In fact, he went so far as to blame left-handedness on inept mothers and nurses who failed to adequately school their children in the correct way of doing things. Aristotle, on the other hand, believed that a person's handedness was natural and inherited.

Even before Plato, the Pythagoreans listed ten first principles, each of which consisted of pairs of opposites, and it comes as no surprise that right is listed on the same side as male, straight, light, good, etc, while left is listed alongside female, crooked, darkness and evil. The early Greek philospher Anaxagoras concluded, mysteriously, that sperm from the left testicle produced girl children, while sperm from the right produced boys, a persistent idea that led to centuries of painful and ineffectual attempts at genetic manipulation. Alexander the Great (usually labelled a left-hander himself, although without evidence) claimed to have conquered a country of left-handed people, although the claim is unsubstantiated.

The influential Ancient Romans were also very pro-right-handedness. According to some, wearing a wedding ring on the third finger of the left hand originated with the Romans, the idea being to fend off evil associated with the left-hand (or, possibly, the widely held belief that that finger was directly connected to the heart by a “love vein”). The modern practice of shaking right hands in greeting dates back to the Roman custom of touching right hands to demonstrate the absence of hidden weapons. Cynics claim that this ritual was positively encouraged by the notoriously paranoid Julius Caesar (who is also widely believed to have been left-handed, although again without evidence) .

Interestingly, Ancient China had some very different beliefs regarding left and right, particularly as regards the Chinese dichotomy of yin and yang. Yin was associated with femininity, submission, blood and earth, but also with the right side, while yang was associated with masculinity, leadership, light, the sun and, perhaps surprisingly, the left side. Notwithstanding, though, China would go on to become one of the most outspoken protectors of right-handed dominance.