The zoo was founded in 1926 by a three-member commission led by Stanko Karaman.

When it opened, the zoo covered only 4 hectares (10 acres), and exhibited only a few animals which it had received as gifts.

With a decision by the Skopje city council in 1965, and the new town zoning in 1966, the zoo was expanded to its current size.

The only elephant ever held by the zoo died at age 23 less than a year after being transferred from the Belgrade Zoo,[2] and the chronically depressed lone Chimpanzee Koko was transferred to the AAP Primate Sanctuary in 2009.

[3][4] On 19 October 2024, a case of bird flu of the H5N1 variant was detected in a deceased goose at a pond in the zoo, prompting the complex's closure for three weeks and the culling of several birds that also lived in the pond.