The cultivation of tobacco usually takes place annually. The tobacco is germinated in cold frames or hotbeds and then transplanted to the field until it matures. It is grown in warm climates with rich, well-drained soil. About 4.2 million hectares of tobacco were under cultivation worldwide in 2000, yielding over seven million tonnes of tobacco.

Tobacco seeds are scattered onto the surface of the soil, as their germination is activated by light. In colonial Virginia, seedbeds were fertilized with wood ash or animal manure (frequently powdered horse manure). Seedbeds were then covered with branches to protect the young plants from frost damage, and the plants were left alone until around April.

In the 19th century, young plants came under increasing attack from certain types of flea beetles, Epitrix cucumeris or Epitrix pubescens, which destroyed half the U.S. tobacco crops in 1876. In the years afterward, many experiments were attempted and discussed to control the flea beetle. By 1880, growers discovered that replacing the branches with a frame covered with thin fabric effectively protected plants from the beetle. This practice spread, becoming ubiquitous in the 1890s.

In Asia, Oceania, and the Indian subcontinent, the tobacco cutworm (Spodoptera litura) is a great pest to the tobacco plant. The caterpillar's vigorous eating habits can cause up to 23-50% in yield losses, resulting in economic strain to the local agricultural economies. The cabbage looper is also known to have caused damage to tobacco plants in North Carolina, which became a concern as farmers lacked a suitable method for controlling the caterpillars.

Shade tobacco is the practice of growing the plants under a screen of cheesecloth fabric. The thin leaves were used for the outer wrappings of cigars.

Tobacco can be harvested in several ways. In the oldest method, the entire plant is harvested at once by cutting off the stalk at the ground with a sickle. In the nineteenth century, bright tobacco began to be harvested by pulling individual leaves off the stalk as they ripened. As the plants grow, they usually require topping and suckering. "Topping" is the removal of the tobacco flowers while "suckering" is the pruning out of leaves that are otherwise unproductive. Both procedures ensure that as much of the plant's energy as possible focuses on producing the large leaves that are harvested and sold. "Cropping", "Pulling", and "Priming" are terms for removing mature leaves from tobacco plants. Leaves are cropped as they ripen, from the bottom to the top of the stalk.

The first crop of leaves located near the base of the tobacco stalk are called "sand lugs" in more rural southern tobacco states. They are called "sand lugs" because these leaves are close to the ground and get splashed with sand and clay when heavy rains hit the soil. Sand lugs weigh the most, and are most difficult to work with. Their weight is due to their large size and the added weight of soil; slaves lugged each stack to the "stringer" or "looper", typically a female slave, who bundled each stack of leaves. Eventually, workers carried the tobacco and placed it on sleds or trailers.

As the industrial revolution approached America, the harvesting wagons that transported leaves were equipped with man-powered stringers, an apparatus that used twine to attach leaves to a pole. In modern times, large fields are harvested by a single piece of farm equipment, though topping the flower and in some cases the plucking of immature leaves is still done by hand.