Urea was first discovered in urine in 1727 by the Dutch scientist Herman Boerhaave, although this discovery is often attributed to the French chemist Hilaire Rouelle.

Boerhaave used the following steps to isolate urea:

1. Boiled off water, resulting in a substance similar to fresh cream

2. Used filter paper to squeeze out remaining liquid

3. Waited a year for solid to form under an oily liquid

4. Removed the oily liquid

5. Dissolved the solid in water

6. Used recrystallization to tease out the urea

In 1828, the German chemist Friedrich Wöhler obtained urea artificially by treating silver cyanate with ammonium chloride.

• AgNCO + NH₄Cl → (NH₂)₂CO + AgCl

This was the first time an organic compound was artificially synthesized from inorganic starting materials, without the involvement of living organisms. The results of this experiment implicitly discredited vitalism — the theory that the chemicals of living organisms are fundamentally different from those of inanimate matter. This insight was important for the development of organic chemistry. His discovery prompted Wöhler to write triumphantly to Berzelius: "I must tell you that I can make urea without the use of kidneys, either man or dog. Ammonium cyanate is urea." In fact, this was incorrect. These are two different chemicals, which are in chemical equilibrium heavily favoring urea under standard conditions. Regardless, with his discovery, Wöhler secured a place among the pioneers of organic chemistry.