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Vrubel started to draw at an early age. However he entered the Law Faculty of St. Petersburg University from which he graduated in 1880. The following year, he began to attend the Imperial Academy of Fine Arts. In the Academy, he studied under Pyotr Chistyakov and Ilya Repin and became friends with artist Valentin Serov. He ardently devoted himself to the study of art and would often draw 12-14 hours a day. His early drawings already bear the mark of an extraordinary talent. Such is the case of Anna Karenina’s Visit with Her Son, a composition charged with an unmistakable passion.

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After his graduation from the Academy of Fine Arts, he was asked to help with the restoration of the 12th century St. Cyril church in Kiev. While living in Kiev in 1884-1889, he experienced the influence of Medieval and especially Byzantine art. In particular, he discovered that the two-dimensional character of Byzantine mosaics only contributed to their strength.

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In 1889, Vrubel moved to Moscow where he became friends with Savva Mamontov, an affluent industrialist and patron of arts. Demon Seated (1890) was the first large canvas, which, though vehemently criticized by contemporaries, elevated Vrubel to a whole new plane of artistic expression. Vrubel had developed the theme of Demon, a hero of Mikhail Lermontov’s poem, from 1885. With Vrubel, Demon becomes the incarnation of the romantic spirit. Demon starts out full of hope, searching for harmony and truth, beauty and love. For a brief moment, he even seems to find what he longs for. But eventually his hopes are crushed. He becomes disillusioned and boils with rebellion. In the end, he himself is crushed and thrown out. This world has no place for him.

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In 1890, Vrubel became member of the Abramtsevo circle of Savva Mamontov. In 1890-91, he produced a series of illustrations to Lermontov’s prose and verse for a special edition commemorating the 50th anniversary of the writer’s tragic death. Some of these watercolors bear witness to Vrubel’s appreciation for Arabic and Persian decorative arts. In 1895, Vrubel planned to take part in the 22nd exhibit of the Itinerants but was rejected. He concentrated on developing set design and costumes for the Russian Private Opera of Savva Mamontov and met opera singer Nadezhda Zabela whom he married a year later. Their wedding took place in Geneva, Switzerland.

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In 1900, Vrubel became member of the World of Art group. The same year, he produced some of his best canvases, including The Swan Princess and Lilacs. The Swan Princess was inspired by the opera The Tale of Tsar Saltan by Rimsky-Korsakov in which Zabela-Vrubel sang the role of the Swan Princess. Vrubel said that he placed the figure of Tatiana from Pushkin’s poem Eugene Onegin in Lilacs. Both canvases capture the fleeting atmosphere of twilight and reveal the romantic aspirations of the artist.

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In 1902, he strove to complete his large canvas Demon Overthrown. The canvas was on display at the World of Art exhibition while the unsatisfied painter continued to work on Demon’s face, which looked different each day of the exhibition.

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It was also in 1902 that the first signs of mental trouble began to manifest. Vrubel’s son, Savva, named after Savva Mamontov, died in 1903. Vrubel's mental illness became severe in 1905. The portrait of poet Valery Brusov, dated 1906, was his last large work before he completely lost his sight. In the following extremely difficult years, his sister and wife would read and sing for him.

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In 1906, Sergey Diaghilev took Vrubel’s works to be displayed in Paris, France, where they were admired by the young Pablo Picasso.

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In the winter of 1910, Vrubel deliberately stood before an open window and caught a cold. The same year he died from pneumonia and was buried in St. Petersburg. His wife, Nadezhda Zabela-Vrubel, outlived him only by three years.