Saint Laurent Boulevard's cardinal direction, on a pseudo north–south axis strongly deported to the west, and aligned with the summer solstice's setting sun, was outlined by the Sulpicians towards the end of the 17th century.

In the early 18th century, when the lords of Montreal decided to develop agricultural land further north on the island, they prolonged this little street to build a King's Way exactly along the same axis and named it Chemin Saint-Laurent.

"[4] All day long, St. Lawrence Boulevard, or Main Street, is a frenzy of poor Jews, who gather there to buy groceries, furniture, clothing and meat.

The street reeks of garlic and quarrels and bill collectors: orange crates, stuffed full with garbage and decaying fruit, are piled slipshod in most alleys.

Middle-class members of the community were already beginning to move up the Main towards Sherbrooke and Prince Arthur Streets, while further west, a small number of well-off Jews lived near McGill University.

Despite Canada's poor record of Jewish immigration between 1933 and 1948, Montreal became home to the world's third-largest concentration of Holocaust survivors, most of them Yiddish speakers.

In 1907 a young Polish Jewish immigrant, Hirsch Wolofsky, started the Yiddish-language daily newspaper Keneder Adler (English: Canadian Eagle).

Fred Rose represented the Main's Cartier riding until 1947, when he was expelled from the House of Commons after a controversial conviction on charges of spying for the Soviet Union.

[15] Another supermarket, Warshaw's, was the subject of controversy when the city of Montreal was forced to pay damages after first approving and then rejecting changes to its iconic storefront.

[16] The exterior signage for Warshaw's is on permanent display as part of the Montreal Signs Project at Concordia University's Loyola campus.

Novelists Mordecai Richler, Rejean Ducharme and Michel Tremblay and poets Irving Layton, A. M. Klein and Leonard Cohen were all influenced by this area.

Montreal singer Cœur de pirate's 2011 album Blonde includes a song entitled "Saint-Laurent" that refers to the street.

Saint Laurent Boulevard is also mentioned in The Blacklist (2013), as the location where Raymond 'Red' Reddington (played by James Spader) takes Agent Elizabeth 'Lizzy' Keen (Megan Boone) to meet his liaison for the next attack, within the second episode of the first season, entitled "The Freelancer".

[21] In early June, Saint-Laurent Boulevard becomes the host of the MURAL Festival, an international public art event that attracts artists from all over the world.

Since 2003, Montreal bike couriers organise an illegal time trial race named Beat the Main where dozen of cyclists dash the entire 11.5 km (7 mile) stretch between rue de la Commune and boulevard Gouin, mostly ignoring traffic lights and regulations.