Tobacco was long used by various indigenous groups that lived in the Americas. The Columbian exchange introduced tobacco to the Europeans, and it became an addictive, lucrative and heavily traded commodity. Following the Industrial Revolution, cigarettes became hugely popular worldwide. In the mid-20th century, medical research demonstrated severe negative health effects of tobacco smoking such as lung cancer, which led to governments adopting policies to force a sharp decline in tobacco use.

The tobacco plant, first used by the native people of the Americas, later came into use in Europe and in the rest of the world. Archaeological finds indicate that humans in the Americas began using tobacco as far back as 12,300 years ago, thousands of years earlier than previously documented.

Tobacco had already long been used in the Americas by the time European visitors arrived and took the practice across the Atlantic, where it became popular. Eastern North American tribes have historically carried tobacco in pouches as a readily accepted trade item, as well as smoking it in pipe ceremonies, whether for sacred ceremonies or those to seal a treaty or agreement.

In addition to use in spiritual and religious ceremonies, tobacco is also used in indigenous traditional-medicine systems for the treatment of physical conditions. As a pain killer it has been used for earache and toothache and occasionally as a poultice. Some indigenous peoples in California have used tobacco as the base ingredient in smoking mixtures used for treating colds; usually it is mixed with other traditional medicinals such as Salvia dorrii or Lomatium dissectum (the addition of which was thought to be particularly good for asthma and tuberculosis). Tobacco was also heavily cultivated in the Chesapeake Colonies area from the 1620s on, where it was sometimes used as a form of currency.

According to Iroquois mythology, tobacco first grew out of Atahensic's head after she died giving birth to her twin sons, Sapling and Flint.

Religious use of tobacco is still common to this day amongst many indigenous peoples, particularly in the Americas. Among the Cree and Ojibwe of Canada and the north-central United States, it is offered to the Creator, with prayers, and is used in sweat lodges and pipe ceremonies, and presented as a gift. A gift of tobacco is traditional when asking an Ojibwe elder a question of a spiritual nature.

Tobacco was completely unfamiliar to Europeans before the discovery of the New World. Bartolomé de las Casas described how the first scouts sent by Christopher Columbus into the interior of Cuba found:

men with half-burned wood in their hands and certain herbs to take their smokes, which are some dry herbs put in a certain leaf, also dry, like those the boys make on the day of the Passover of the Holy Ghost; and having lighted one part of it, by the other they suck, absorb, or receive that smoke inside with the breath, by which they become benumbed and almost drunk, and so it is said they do not feel fatigue. These, muskets as we will call them, they call tabacos. I knew Spaniards on this island of Española who were accustomed to take it, and being reprimanded for it, by telling them it was a vice, they replied they were unable to cease using it. I do not know what relish or benefit they found in it.