A chemical substance is a form of matter that has constant chemical composition and characteristic properties. It cannot be separated into components by physical separation methods, i.e., without breaking chemical bonds. Chemical substances can be chemical elements, chemical compounds, ions or alloys.

Chemical substances are often called 'pure' to set them apart from mixtures. A common example of a chemical substance is pure water; it has the same properties and the same ratio of hydrogen to oxygen whether it is isolated from a river or made in a laboratory. Other chemical substances commonly encountered in pure form are diamond (carbon), gold, table salt (sodium chloride) and refined sugar (sucrose). However, in practice, no substance is entirely pure, and chemical purity is specified according to the intended use of the chemical. Chemical substances exist as solids, liquids, gases or plasma, and may change between these phases of matter with changes in temperature or pressure. Chemical substances may be combined or converted to others by means of chemical reactions. Forms of energy, such as light and heat, are not considered to be matter, and are thus not "substances" in this regard.

A chemical substance (also called a pure substance) may well be defined as "any material with a definite chemical composition" in an introductory general chemistry textbook. According to this definition a chemical substance can either be a pure chemical element or a pure chemical compound. But, there are exceptions to this definition; a pure substance can also be defined as a form of matter that has both definite composition and distinct properties. The chemical substance index published by CAS also includes several alloys of uncertain composition. Non-stoichiometric compounds are a special case (in inorganic chemistry) that violates the law of constant composition, and for them, it is sometimes difficult to draw the line between a mixture and a compound, as in the case of palladium hydride. Broader definitions of chemicals or chemical substances can be found, for example: "the term 'chemical substance' means any organic or inorganic substance of a particular molecular identity, including – (i) any combination of such substances occurring in whole or in part as a result of a chemical reaction or occurring in nature"

In geology, substances of uniform composition are called minerals, while physical mixtures (aggregates) of several minerals (different substances) are defined as rocks. Many minerals, however, mutually dissolve into solid solutions, such that a single rock is a uniform substance despite being a mixture in stoichiometric terms. Feldspars are a common example: anorthoclase is an alkali aluminium silicate, where the alkali metal is interchangeably either sodium or potassium.