The Polish architect Władysław Horodecki originally constructed the House with Chimaeras for use as his own upmarket apartment building during 1901–02.

However, as the years went by, Horodecki eventually had to sell the building due to financial troubles, after which it changed ownership numerous times before finally being occupied by an official Communist Party polyclinic until the early 2000s.

[3] When the building was vacated, its interior and exterior decor were fully reconstructed and restored according to Horodecki's original plans.

[4] The building derives its popular name from the ornate decorations depicting exotic animals and hunting scenes, which were sculpted by Italian architect Emilio Sala, since Horodecki was an avid hunter.

[5] At the time of the building's construction, Horodecki had already established himself as a prominent Kyiv architect, having designed and constructed together with his close friend and partner engineer Anton Strauss many city buildings, from the St. Nicholas Roman Catholic Cathedral to the Karaite Kenesa and what today is the National Art Museum of Ukraine.

[8][nb 2] Horodecki bought the first lot of land on February 1, 1901, with construction work commencing on March 18 of that year.

A cowshed was located on the premises due to Horodecki's insistence on fresh in-house milk,[4][9] though it was specifically placed in a way that the smell of the cows would not disturb the tenants.

Due to financial mismanagement which included his Safari hunting hobby,[4] in July 1912, Horodecki pledged the building as a collateral against a loan taken from Kyiv Mutual Credit Association.

In order to force the occupants out of the building, the workers boarded up all of the windows and threatened to do the same to the doors if the polyclinic did not vacate the premises.

[16] The Council also allowed the Ukrainian government to construct a new square (closing off all automobile traffic) in front of the building for use in official ceremonies.

Horodecki featured such motifs in the building's exterior decor in the forms of mythical creatures and big-game animals.

The Italian sculptor Emilio Sala was responsible for both the internal and external sculptural decorations, such as mermaids, dolphins, and frogs on the roof of the building, sinking ships and hunting trophies on the exterior walls, and exuberant interior decorations, such as grand stairways and chandeliers depicting huge catfish strangled in the stems of lotus flowers.

The open floor plan and extra rooms featured throughout the building are characteristic of the houses of the wealthy of the early 20th century.

[13] On the lowest level of the building, which is located deep in the hill, were two stables, two rooms for coachmen, a shared laundry, and two separate apartments.

[nb 7] The apartment on the top floor had one less room; to make up for this, there was a connecting terrace which provided a panoramic view of the city.

[8][nb 8] Throughout the years, the unusual nature of the House with Chimaeras has given rise to a number of stories occasionally repeated in guide-books or newspapers, which are however either untrue or lacking any verifiable source.

[24] According to the first legend, Władysław Horodecki's daughter had committed suicide jumping into Dnieper River either because of some unfortunate love affair or because of a family feud.

[25] According to the third legend, Horodecki had cursed it in 1913 (due to his inability to repay his creditors); all of the house's tenants would be either unhappy or would meet some sort of financial misfortune.