Contact herbicides kill only the parts of the plant they touch; systemic herbicides are absorbed by foliage or roots and translocated to other parts of the plant. Preemergence herbicides, mixed into the soil, will kill germinating seeds and small seedlings. Postemergence herbicides either hinder photosynthesis or inhibit growth.

Early chemical herbicides were inorganic compounds. Herbicides such as ashes, common salts, and bittern have been used in agriculture since ancient times. Observation in 1896 that Bordeaux mixture, a fungicide, also provided control of certain weeds, led to the use of copper sulfate as a selective weed killer to control charlock (wild mustard) in cereals. By 1900, solutions of sulfuric acid, iron sulfate, copper nitrate, and ammonium and potassium salts were known to act as selective herbicides; soon thereafter sodium arsenite solutions became the standard herbicides, and they were used in large quantities until about 1960. Other inorganic herbicides include ammonium sulfamate, carbon bisulfide, sodium chlorate, sulfuric acid solutions, and formulations containing borate.

Organic herbicides began to be produced in earnest with dinitrophenol compounds in 1932. A breakthrough occurred in the 1940s with 2,4-D (2,4-dichlorophenoxyacetic acid), a compound similar to plant hormones, which is a highly selective systemic herbicide when used in very small quantities. 2,4-D was quickly adopted to control broad-leaved weeds in corn, sorghum, small grains, and grass pastures, as well as in lawns and other ornamental turf. The phenoxyaliphatic acids and their derivatives, another major group of organic herbicides, succeeded because of their selectivity and ease of translocation. Other groups of organic herbicides include organic arsenicals, substituted amides and ureas, nitrogen heterocyclic acids, phenol derivatives, triazines, and sulfonylureas.

In the 1960s and 1970s, a combination of 2,4-D and 2,4,5-T was widely used in Vietnam as a defoliant under the name Agent Orange. As a result of questions concerning the possible health effects of the use of Agent Orange, heightened awareness of possible ecological and health dangers attributable to herbicides has resulted in reevaluation of many compounds and has called indiscriminate use into question. Use of the dioxin-containing 2,4,5-T was prohibited in the United States in 1984. In 1975, Mexico, at the urging of the United States government, began spraying fields of marijuana with paraquat, which both eliminated the crop and raised fears of toxic side effects in marijuana users.

Glyphosate, a compound first identified as a herbicide in 1970 and sold beginning in the 1970s under the tradename Roundup, has been widely used as a broad-spectrum weedkiller because of its relatively low toxicity and tendency to degrade relatively quickly in the environment. Beginning in the 1990s, the use of crop strains that were resistant to its herbicidal effects also contributed to widespread use. In the early 21st cent., however, such use led to the development of so-called superweeds that had developed resistance to glyphosate.

See also pesticide.