Melamine was first synthesized in 1834 by German chemist Justus von Liebig. In early production, calcium cyanamide is first converted to dicyandiamide, which is heated above its melting temperature to produce melamine. Today, most industrial manufacturers use urea to produce melamine in the following reactions:

6 (NH2)2CO → C3H6N6 + 6NH3 + 3CO2

In the first step, urea breaks down into cyanic acid and ammonia:

(NH2)2CO → HNCO + NH3

Cyanic acid is polymerized to cyanuric acid, which condenses with the released ammonia to form melamine. The released water reacts with cyanic acid, which helps drive the reaction:

6 HNCO + 3NH3 → C3H6N6 + 3CO2 + 3NH3

These reactions can be carried out by either of two methods: catalytic gas phase production or high pressure liquid phase production. In one method, molten urea is introduced onto a fluidized bed with a catalyst for the reaction. Hot ammonia gas is also present to fluidize the bed and inhibit deamination. The effluent is then cooled. Ammonia and carbon dioxide in the exhaust gas are separated from the slurry containing melamine. The slurry is further concentrated and crystallized to produce melamine. Major manufacturers and licensors such as Orascom Construction Industries, BASF and Eurotecnica have developed proprietary methods.

The exhaust gas contains a lot of ammonia. Therefore, melamine production is usually combined with urea production using ammonia as raw material.

Crystallization and washing of melamine produce a large amount of wastewater, which may be concentrated into solids (1.5-5% by weight) for easy treatment. Solids can contain approximately 70% melamine, 23% oxytriazine (melamine, melamine and cyanuric acid), and 0.7% polycondensation (melamine, melamine and melon). In the Eurotecnica process, however, there is no solid waste, and the pollutants are broken down into ammonia and carbon dioxide, which are delivered as exhaust gas to the upstream urea unit; Therefore, the wastewater can be recycled to the melamine plant itself or used as a clean cooling water recharge.

Melamine reacts with acids and related compounds to form cyanuric acid melamine and related crystal structures, which are considered as contaminants or biomarkers in protein adulteration in China.