Spadina Avenue runs south from Bloor Street to the Gardiner Expressway, just north of Lake Ontario.

[1] The /aɪ/ variation is now predominant among most Torontonians, to the point that in 2011 a minor controversy emerged when the Toronto Transit Commission's new automated announcement system pronounced the upcoming subway stop with /iː/.

[1] The name originates from the Ojibwa word ishpadinaa,[2] meaning "high place/ridge"[3] or "sudden rise in the land.

For a number of decades, Spadina Avenue and nearby Kensington Market were the centre of Jewish life in Toronto with the area around Spadina being the home of the garment district—where many Jews worked—as well as numerous Jewish delis, tailors, bookstores, cinemas, Yiddish theatres, synagogues and other political, social and cultural institutions.

In the 1990s, however, the TTC rebuilt and reinstated the 510 Spadina streetcar line, which runs largely in a dedicated right-of-way along the median strip of the street since its opening in 1997.

In 2006, the Forest Hill Jewish Centre announced plans to rebuild the façade of the Great Synagogue of Jasło, Poland, which was destroyed by the German Army in World War II, as the façade of its new building on Spadina Road, a project that was completed by 2015.

[6][7] The southern section of Spadina was the heart of Toronto's industrial area for most of the 20th century, but in the 1970s, most of the factories left.

North of Queen Street West, the avenue passes along the eastern side of the Alexandra Park neighbourhood, which is made up of a number of public housing projects.

The intersection of Spadina Avenue and College Street is known as an inexpensive place to buy electronics, with a number of independent stores in the area.

It is also the location of the El Mocambo, where the Rolling Stones performed one night to a small audience that included the wife of Prime Minister Pierre Trudeau.

Just north of College Street, the roadway splits into a traffic circle, called Spadina Crescent.

The house and the street are named after the escarpment, the word ishpadinaa meaning "[it is a] hill" or "rise" in the Ojibwe language.

Starting north of St. Clair Avenue and continuing a few blocks further north is lower Forest Hill Village, which forms the main street of a small commercial area, the historical downtown of Forest Hill before Toronto grew around the town.

North of Eglinton Avenue, Spadina Road is again interrupted, here by the trenched right-of-way for the defunct Belt Line Railway, now a popular walking trail.