South Lake Union (sometimes SLU) is a neighborhood in central Seattle, Washington, so named because it is at the southern tip of Lake Union.

The official boundaries of the City of Seattle Urban Center are Denny Way on the south, beyond which is Denny Triangle; Interstate 5 on the east, beyond which is Capitol Hill; Aurora Avenue N. (State Route 99) and 7th Avenue N. on the west, beyond which is Lower Queen Anne; and Galer Street, Lake Union, and E. Newton Place on the north, beyond which are Westlake and Eastlake, but like most Seattle neighborhoods, its precise boundaries are indeterminate. In particular Cornish College of the Arts and Vulcan Inc. properties such as 2200 and 2201 Westlake are officially in Denny Triangle for city planning and zoning purposes but often referred to as South Lake Union. The portion of South Lake Union east of Fairview Avenue N. is historically known as Cascade. Historic structures continue to stand in the Cascade neighborhood today.

Its main thoroughfares are Valley and Mercer Streets (east- and westbound) and Dexter, 9th, Westlake, and Fairview Avenues N. and Eastlake Avenue E. (north- and southbound). The city addressed transportation issues by changing Mercer Street into a two-way, six-lane, tree-lined boulevard, with Valley Street becoming a two-way, pedestrian friendly road.

Lake Union is known in Chinook Jargon as Tenass Chuck ("little water", as against Lake Washington, Hyas Chuck, "big water"). It is similarly known in Duwamish as meman hartshu, "little lake". When white pioneers arrived in the 1850s, Native Americans—probably Duwamish or Southern Coast Salish—were encamped near the southwest corner of the lake and along a stream near the present-day corner of 8th and Thomas; another stream ran near Boren Avenue. There was a trail from the south end of the lake to Elliott Bay. At the time, there were deer and elk in the area; natives also ate fish, clams, root vegetables, camas, bracken, wapato and berries. Significant native settlement in South Lake Union lasted until 1875, when a windstorm knocked over a tree, destroying a longhouse in what is now Cascade.

Pioneer David Denny (of the Denny Party) staked a claim in 1853. Denny's claim ran from South Lake Union (where the lake extended farther to the south and west than it does today) south to what is now Denny Way and west to include the area that is now the Seattle Center grounds. In 1882, the Lake Union and Lumber Company established a sawmill (the city's largest) on the south shore of the lake, near what is now the corner of Mercer and Westlake; Denny bought it in 1884, renaming it the Western Mill. He cleared the land along the south shore of the lake and, in 1885, cut a weir from Portage Bay at the northeast corner of the lake to Lake Washington, which allowed logs to be floated to Lake Union, so that the entire area of the larger Lake Washington was a catchment for his mill.

Denny operated the Western Mill until 1895, and many of his employees settled nearby, some with families. During this time other mills opened in the area. In addition, the lake became a link in the transport of coal, which came from near Issaquah via Lake Washington, wagon to Portage Bay and thence to Lake Union. At first, coal was transported from South Lake Union to the downtown docks by wagon, then from 1872 to about 1877 on a narrow-gauge railroad that followed the route of present-day Westlake Avenue to Pike Street. The railroad, however, was abandoned, and the route degenerated back to a wagon trail.

After David Denny's bankruptcy 1895, this mill operated until the 1920s under new ownership of Brace / Hergert Mill Company. In 1909 Brace & Hergert extended their mill into the lake building a peninsula, now known as Lake Union Park. The last remaining portion of the mill business was Brace Lumber Company which operated from 1925 to 1988, the end of the mill era. The area also saw a growth in manufacturing toward the turn of the century. Cabinetry and furniture led the way in the 1890s, followed by shipbuilding, Bill Boeing's first airplane factory, manufacturing seaplanes and, in Cascade, Seattle City Light's Hydro House (1912) and Lake Union Steam Plant (1914) and the first Ford Model T assembly plant west of the Mississippi River (1914). Both of these buildings now have landmark status. The former steam plant now houses Zymogenetics and the former Ford building is used for rental storage space. Meanwhile, the Northern Pacific Railway ran a railroad line around Lake Union and down Terry Avenue, where a freight station opened in 1913.

With industrial and commercial growth, more residential centers sprang up to house company employees and other residents. Preeminent among these residential centers was Cascade. At the center of the community established by the Russians, Swedes, Norwegians, and Greeks who settled there in the late 19th and early 20th centuries was the Cascade School (built 1894; demolished after the 1949 Olympia earthquake), a public elementary school from which the neighborhood took its name. From the 1930s, South Lake Union became less residential, evolving into an area of small business, warehouses and auto-oriented services. Cascade slowly lost its identity as a neighborhood distinct from the rest of South Lake Union, especially after construction of Interstate 5 cut it off from Capitol Hill.