He was a pupil of Pio Sanquirico. Pellizza used a divisionist technique in which a painting is created by juxtaposing small dots of paint according to specific color theory.
His most famous work, Il Quarto Stato ("The Fourth Estate"), has become a well-known symbol for progressive and socialist causes in Italy, and throughout Europe. The painting is shown during the opening credits of Bernardo Bertolucci's film 1900.
Pellizza hanged himself, in 1907, after the deaths of his wife and son.