After his painting was rejected by the Paris Salon, Seurat turned away from such establishments, instead allying himself with the independent artists of Paris. In 1884 he and other artists (including Maximilien Luce) formed the Societe des Artistes Independants. There he met and befriended fellow artist Paul Signac. Seurat shared his new ideas about pointillism with Signac, who subsequently painted in the same idiom. In the summer of 1884 Seurat began work on his masterpiece, Sunday Afternoon on the Island of La Grande Jatte, which took him two years to complete.

Later he moved from the Boulevard de Clichy to a quieter studio nearby, where he lived secretly with a young model, Madeleine Knobloch. In February 1890 she gave birth to his son. It was not until two days before his death that he introduced his young family to his parents. Shortly after his death, Madeleine gave birth to his second son, whose name is unknown, and who died at birth or soon after.

The cause of Seurat's death is uncertain, and has been attributed to a form of meningitis, pneumonia, infectious angina, and/or diphtheria. His last ambitious work, The Circus, was left unfinished at the time of his death.