The street, laid out as part of Colonel Light's city plan in 1837,[2] was named after George Grote, an English classical historian and supporter of Robert Gouger.

A much larger building, designed by Woods Bagot, was built between 1912 and 1914, and still stands today, on the corner of Gary Street.

[4] A chapel was built on the northern side of Grote Street at the eastern end for the Church of Christ congregation in December 1856.

Although not financially supported by the colonial government, it was funded by various private donations by parliamentarians, including Richard Chaffey Baker, George Charles Hawker, and John Howard Angas.

Apart from his large retail stores, Bruce ran what were known as "cheapjack" stalls at the market, basically a type of lottery or "sixpenny dip", where buyers would offer a coin for an unknown purchase.

[14] Bruce had a successful career as a businessman though the 1910s, establishing a number of stores in Adelaide and country towns, as well as breeding pigs.

He had a 14,000-acre (5,700 ha) farm near Renmark, South Australia, and was described in The Advertiser as one "who has long been recognised as one of Adelaide's leading business magnates".

[22] There was still a business concern named W. H. Bruce in 1954, which opened a new food store (of meats) at 13–15 Grote Street in December 1954.

[23] In 1931, an arcade was constructed through the shops formerly leased by Bruce, to create a northern entrance to the Adelaide Central Market.

[26] The Lyric Theatre was a cinema built by owner W. H. Bruce, completed during a builders' labourers' strike in 1912 by paying the men the wages asked for by their union.

The Grote Street–Sir Donald Bradman Drive route is the most direct method of travelling from the CBD to the Adelaide Airport.

A paifang, comprising an archway erected by the city council and two lions donated by the People's Republic of China, marks the northern entrance to the Chinatown.

[4] St Patrick's Church, Her Majesty's Theatre, and the rear entrance of the Adelaide Central bus station are located on this street.

[4] Since the 21st century, Grote Street has become the home of various businesses selling items relating to housing construction and renovation, such as tiles, built-in furniture, and bedding.