Willem Witsen grew up on the Prinsengracht and Westeinde in Amsterdam. From 1876 to 1884 he took drawing lessons at the Rijksakademie van Beeldende Kunsten in that city. There he became friends with painters such as Willem Tholen, Jacobus van Looy, Jan Veth, Eduard Karsen and Jan Toorop, and later also with George Breitner and Isaac Israels. After a stay in London from 1888-1891, where he became acquainted with Whistler's work, Witsen started painting dreamy, tranquil cityscapes in a dark colour. These cityscapes, which capture the mood and timeless beauty of the city, are the highlight of his work. In contrast to the busy city impressions of Breitner and Israels, Witsen saw Amsterdam as a monument of timeless beauty. Like Breitner, Witsen was a photographer, which explains his special way of looking. After 1910 he painted many of his Amsterdam cityscapes from the water. He had a barge with a management hut at the Montelbaanstoren that served as a floating studio. From 1911 he exchanged it for a deck barge with a shack that he had moved to places where he wanted to work.
Witsen, who belonged to the Tachtigers – a group of artists active in the 1880s – often worked at Ewijckshoeve, the family home near Lage Vuursche, until 1884. His Amsterdam friends, young, ambitious artists who considered themselves great innovators in art and literature, were always welcome there. But it was also a place where Witsen could escape the dynamics of the big city and focus on nature undisturbed. From April 1887 he returned to Amsterdam and used the studio of his friend George Breitner at Oude Schans 5 in Amsterdam for a few months, overlooking the Montelbaanstoren.
In 1893 Witsen married the poet and writer Betsy van Vloten, whom he had met through her brother-in-law Frederik van Eeden. They moved to Ede, where they had three sons. However, the marriage was dissolved in 1902 and five years later Witsen married Marie Schorr. He settled with her again in Amsterdam at Oosterpark 82, the house where he used to have a studio with Breitner and Isaac Israels, but which the couple would live in as a whole from 1906 and would become known as the Witsenhuis. Witsen became a much sought-after portrait painter and also started painting still lifes. With his wife he undertook numerous trips, not only within Europe, but also overseas, to San Francisco and Canada and in 1921/1922 the Dutch East Indies. Shortly afterwards, in 1923, Witsen died as a result of a respiratory infection in Amsterdam.
Witsen was not only a painter and etcher, in 1885 he founded the Dutch Etching Club together with two art enthusiasts, but also a photographer. This interest arose during his stay in London from the end of 1888. He sometimes also used the photographs he took to make paintings in his studio, which explains the low viewpoint and the cut-off buildings in his work. Witsen also often photographed his artist friends and family in all kinds of moods. He always took his camera with him on his travels through Europe and although he was not trained as a photographer, he had his own approach in which strong light-dark contrasts were important to him.