Blek began his artwork in 1981 and painted rat templates on the walls of Parisian streets. He described the rat as "the only free animal in the city" and a rat that "spreads the plague everywhere, just like street art." His name comes from the comic book Blek le Roc, which uses "rat" as a switch for "art".
He was initially influenced by graffiti art in New York after a visit in 1971, but chose a style that better suited Paris, due to the different architecture of the two cities. He was also influenced by the influence of the Canadian artist Richard Hambleton, who painted large human figures in the 1980s. In 1985, he was at the first meeting of the graffiti and urban art movement in Bondy (France) on the initiative of VLP with Speedy Graphito, Kim Prisu, Miss Tic, SP 38, Epsylon Point, Jef Aérosol, Futura 2000, Nuklé-Art, Banlieue-Banlieue. Blek 's oldest surviving street art graffiti work, a 1991 replica of Caravaggio' s Madonna di Loreta, dedicated to his future wife Sybille, was rediscovered for posters on a house wall in Leipzig, Germany in 2012.

The French authorities identified Blek in 1991, when he was arrested while staging a replica of Caravaggio's Madonna with child, and a connection with Blek and his artwork was made by the police. From then on, he worked exclusively with pre-printed posters, mentioning the faster application of the medium to the walls and also the reduction of the sentence if he was caught in the act.
He had a great influence on today's graffiti-art and "guerilla-art" movements, the main motivation of his work was social consciousness and the desire to bring art to people. Many of his works depict lonely individuals in opposition to larger, repressive groups. In 2006, he launched a series of images depicting the homeless, depicting standing, sitting or lying on the sidewalks, in an effort to highlight what he sees as a global problem.

In October 2003, Blek le Rat had his first solo exhibition in the UK in London at the Leonard Street Gallery. He participated in the Cans Festival in 2008, which featured outdoor street painting on a street in Waterloo, London.
His American gallery debut took place at the Subliminal Projects Gallery in Los Angeles in 2008. It included paintings, screen printing, and 3D artwork, as well as photographs by his wife, Sybille Prou.
Blek also had an exhibition in December 2009 at the Melbourne Metro Gallery, a street art center in Australia. The exhibition entitled "Le Ciel Est Bleu, La Vie Est Belle" (The sky is blue, life is beautiful) featured wooden panels, canvases, screen printing and photographs that have followed the artist's work from the early 1980s to the present.
Blek le Rat, however, preferred the streets to galleries, saying that the integrity of the artist should be seen by as many people as possible without being sold or recognized in the museum.
In 2014, Blek le Rat 3 exhibited extensive original paintings and an edition of 25 unique monotypes with lithographs in an environment that combines these traditional spaces - the Quin Hotel in New York - as part of the Quin Arts hotel program.