is manufactured from glycol with yields of 70-80% in a gas-phase oxidation with air. The reaction takes place at over 300°C in the presence of Ag or Cu catalysts and small amounts of halogen compounds to prevent total oxidation:

Another possibility for the synthesis is the oxidation of dehyde with HNO₃, either noncatalytically or with metal salt catalysts. is reacted with 69% HNO₃ under mild conditions at about 40 °C with a maximum yield of about 70%. In addition to the byproducts glycolic acid, oxalic acid, acetic acid and formic acid, about 10% glyoxylic acid is also formed. By raising the temperature and the HNO₃ concentration, the oxidation can be directed to favor glyoxylic acid, which is needed for largescale manufacture of vanillin, ethyl vanillin, and allantoin.

The aqueous glyoxal solution is purified by ion exchange. Since glyoxal is unstable in its pure form, it is used either as a 30-40% aqueous solution or as a solid hydrate with an 80% glyoxal content.