Beksiński had no formal training as an artist. His paintings were mainly created using oil paint on hardboard panels which he personally prepared, although he also experimented with acrylic paints. He abhorred silence, and always listened to classical music while painting.
A prestigious exhibition in Warsaw in 1964 proved to be his first major success, as all his paintings were sold.
Beksiński threw himself into painting with a passion, and worked constantly (always to the strains of classical music). He soon became the leading figure in contemporary Polish art. In the late 1960s, Beksiński entered what he himself called his "fantastic period", which lasted up to the mid-1980s. This is his best-known period, during which he created very disturbing images, showing a surrealistic, post-apocalyptic environment with very detailed scenes of death, decay, landscapes filled with skeletons, deformed figures and deserts. These paintings were quite detailed, painted with his trademark precision. At the time, Beksiński claimed, "I wish to paint in such a manner as if I were photographing dreams".
Despite the grim overtones, Beksiński claimed some of his works were misunderstood; in his opinion, they were rather optimistic or even humorous. For the most part, though, Beksiński was adamant that even he did not know the meaning of his artworks and was uninterested in possible interpretations; in keeping with this, he refused to provide titles for any of his drawings or paintings. Before moving to Warsaw in 1977, he burned a selection of his works in his own backyard, without leaving any documentation on them. He later claimed that some of those works were "too personal", while others were unsatisfactory, and he didn't want people to see them.
The 1980s marked a transitory period for Beksiński. During this time, his works became more popular in France due to the endeavors of Piotr Dmochowski, and he achieved significant popularity in Western Europe, the United States and Japan. His art in the late 1980s and early 1990s focused on monumental or sculpture-like images rendered in a restricted (and often subdued) color palette, including a series of crosses. Paintings in these style, which often appear to have been sketched densely in colored lines, were much less lavish than those known from his "fantastic period", but just as powerful. In 1994, Beksiński explained "I'm going in the direction of a greater simplification of the background, and at the same time a considerable degree of deformation in the figures, which are being painted without what's known as naturalistic light and shadow. What I'm after is for it to be obvious at first sight that this is a painting I made".
In the latter part of the 1990s, he discovered computers, the Internet, digital photography and photomanipulation, a medium that he focused on until his death.
The late 1990s were a very trying time for Beksiński. His wife, Zofia, died in 1998; a year later, on Christmas Eve 1999, his son Tomasz (a popular radio presenter, music journalist and movie translator) committed suicide. Beksiński discovered his son's body. Unable to come to terms with his son's death, he kept an envelope "For Tomek in case I kick the bucket" pinned to his wall.
On 21 February 2005, Beksiński was found dead in his flat in Warsaw with 17 stab wounds on his body; two of the wounds were determined to have been fatal. Robert Kupiec (the teenage son of his longtime caretaker), who later pleaded guilty, and a friend were arrested shortly after the crime. On 9 November 2006 Robert Kupiec was condemned to 25 years in prison, and his accomplice, Łukasz Kupiec, to 5 years by the court of Warsaw. Before his death, Beksiński refused a small loan to Robert Kupiec (a few hundred złotys; approximately $100).
Although Beksiński's art was often grim, he himself was known to be a pleasant person who took enjoyment from conversation and had a keen sense of humor. He was exceptionally modest and somewhat shy, avoiding public events such as the openings of his own exhibitions. He credited music as his main source of inspiration. He claimed not to be much influenced by literature, cinema or the work of other artists, and almost never visited museums or exhibitions. Beksiński avoided concrete analyses of the content of his work, saying "I cannot conceive of a sensible statement on painting". He was especially dismissive of those who sought or offered simple answers to what his work 'meant'.
The town of Sanok, Poland, houses a museum dedicated to Beksiński. A Beksiński museum housing 50 paintings and 120 drawings from the Dmochowski collection, opened in 2006 in the City Art Gallery of Częstochowa, Poland. A 'Beksiński cross', in the characteristic T-shape frequently employed by the artist, stands in the Nevada desert.