Most of Kusama's oeuvre can be traced back to early hallucinations she first had in her childhood of multiplying dots and nets which gradually spread to dominate her universe. These visions developed into obsessive neuroses which fuelled her paintings, sculptures and performances (during which she invariably covered her naked models with painted polka dots). For Kusama, polka dots had the form of the Sun, "signifying masculine energy, the source of life" while also echoing "the form of the moon, symbolising the feminine principle of reproduction and growth". The earliest recorded work in which she incorporated these dots was a drawing in 1939 (age 10), in which the image of a Japanese woman in a kimono, presumed to be the artist's mother, with whom she had a problematic relationship, is covered and obliterated by spots. In A Passage to Another World by Akira Tatehata, who curated the Japanese Pavilion which featured Kusama at the Venice Biennale, he writes "Pink Dots Let Me Rest in a Tomb of Stars is a huge picture constituted of sixteen canvases. Standing in front of it, as far as the eye can see, the viewer is confronted with a myriad of dots that appear to vibrate elaborately through an optical effect. The grandeur of the extensive space is quite fascinating. The dots of various sizes appear to have been proportioned at random but are potentially placed in arcs. That is how the image that seems merely to be covered all over in dots at first sight results in a complicated yet simple composition in which the viewer is left to gaze in all directions. However unemotional Kusama's repetition in perpetual action may be, she does it in response to the sound from the cosmos in an attempt to become part of it."

In 1959, Kusama had her first solo exhibition in New York at the Brata Gallery, a well respected artist's co-op. She showed a series of white net paintings which were enthusiastically reviewed by Donald Judd (both Judd and Frank Stella then acquired paintings from the show). Friends recounted how Kusama, with amazing stamina and concentration would work on her intricate canvases in one complete sitting, painting obsessively for up to 50 or 60 hours until the painting was finished and she collapsed from exhaustion. In an interview with Andrew Solomon in Artforum, she describes working on one of her red net paintings: "in New York I was painting the nets and then I noticed that it spread to the floor and the curtains and to the window so I went to catch the red net and I examined it without noticing at first that my hands were also covered by the red nets and that was the turning point and I began creating sculpture so that I could put the patterns on everything". Solitude of the Earth (1994) is a result of this development: it comprises an installation of two white chairs, a table and a cabinet covered in objects and white netting. As a work it evokes a fetishistic response to female paraphernalia and the trappings of domesticity, while echoing the boring monotonous work of stitching sewing or knitting. Alexandra Munroe writes 'her nets, which she claims separate her from people and reality, are a kind of imposed chastity veil which keeps her from real life, the man's world.'

Judith Kirshner discusses how the discourse around Kusama's "hallucinatory images of an infinite repeating pattern which spreads and multiplies until it obliterates the physical universe underscores her creative process of repetition while under a spell of obsessional compulsion" and nowhere is this more evident than in her Infinity Mirrored Room installations comprising of mirrors and light bulbs which create optical illusions of infinity. She further writes, "formless and spreading over surfaces, her patterns make it difficult to tell where pieces begin or end. As one peeks inside Infinity Mirrored Room Love Forever (1996) what seems delusional becomes kaleidoscopic and by the repeated mirroring of light bulbs, an illusion of endless dots and prisms. Drawn into virtual reality, viewers of this work are denied actual entry and participate only by looking."