In 1878, Camille Monet was diagnosed with uterine cancer. She died on 5 September 1879 at the age of thirty-two. Monet made a study in oils of his dead wife. Many years later, the artist confessed to his friend Georges Clemenceau that his need to analyze colors was both the joy and torment of his life. He explained, "I one day found myself looking at my beloved wife's dead face and just systematically noting the colors according to an automatic reflex!" John Berger describes Monet on her deathbed as "a blizzard of white, grey, purplish paint ... a terrible blizzard of loss which will forever efface her features. In fact there can be very few death-bed paintings which have been so intensely felt or subjectively expressive."

In 1912, he was diagnosed with cataracts in both eyes, a condition he endured until undergoing surgery in 1923. The paintings done while the cataracts affected his vision have a reddish tone, which is characteristic of the vision of cataract victims.

In 1892, he produced what is probably his best-known series, twenty-six views of Rouen Cathedral. In these paintings Monet broke with painterly traditions by cropping the subject so that only a portion of the façade is seen on the canvas. The paintings do not focus on the grand Medieval building, but on the play of light and shade across its surface, transforming the solid masonry.

His own harshest critic, Monet destroyed as many as 500 of his own paintings. His friend and former French Prime Minister Georges Clémenceau told a journalist in 1927 that Monet would attack canvases when he was dissatisfied with his work, destroying them in a quest for perfection.

Monet died of lung cancer on December 5, 1926, at the age of 86 and is buried in the Giverny church cemetery. At his funeral, his long-time friend Georges Clemenceau removed the black cloth draped over the coffin, stating, "No black for Monet!" and replaced it with a flower-patterned cloth.