The grandson of painter Gillis d'Hondecoeter and nephew of Jan Baptist Weenix, Hondecoeter was apprenticed to Weenix when the young artist’s father died. Melchior became a member of the painting guild in The Hague and remained there much of his career. Living on the Lauriergracht, Hondecoeter was surrounded by art dealers and fellow painters. Studying under Weenix gave Hondecoeter opportunity to develop his technique and his use of colour to the full. As well as scenes of birds in strikingly natural attitudes, d'Hondecoeter painted wall hangings with views of buildings and parks although here, too, birds were usually a presence.

Hondecoeter painted near exclusively bird subjects, whether exotic or game, in park-like landscapes or wild surrounds. his paintings feature geese (Brent goose, Egyptian brent and red-breasted brent), fieldfares, partridges, pigeons, ducks, magpies and peacocks, but also African grey crowned cranes, Asian sarus cranes, Indonesian Yellow-crested Cockatoos, an Indonesian Purple-naped Lory and Grey-headed Lovebirds from Madagascar.

Hondecoeter acquired celebrity with his bird depicted as living emotive creatures, whether peaceful and elegantly poised, or reactive and quarrelling. His images were in sharp contrast at that time to traditional depictions of birds by contemporaries who showed gamekeeper's perquisite after a day's shooting, or as stock in a poulterer's shop or kitchen. It was said that Hondecoeter displayed ‘the maternity of the hen with as much tenderness and feeling as Raphael the maternity of Madonnas.’

William III employed Hondecoeter, then popular with the wealthy Netherlandish magnates, to paint the royal menagerie at Het Loo, a painting in which the artist depicted Indian cattle, elephants and gazelles with accuracy. Other of the painter’s works adorned royal castles at Bensberg and Oranienstein.

The artist was bold in his style, nuanced in his use of colour, and a strong draughtsman. In additions to masterpieces in the Mauritshuis and the Rijksmuseum, fine examples are in the collections of the Wallace, London, the Metropolitan Museum, New York, The National Gallery, London, and the Hermitage, St Petersburg. The largest Hondecoeter exhibition to date was held in Berlin in 2010, where 18 of his works were shown.