Perched atop the Niagara Escarpment, the area that became Waterdown has been inhabited for thousands of years. Professor John Triggs of Wilfrid Laurier University found evidence of Algonquin-speaking Aboriginals from as far back as 7,500 BCE.[3] One of the earliest known groups to inhabit the area was the Neutral Confederacy (a name coined by Samuel Champlain because they did not take sides in the conflicts between the Huron and Iroquois Confederacy). By the early 1600s, the powerful chief named Souharissen united the Neutral First Nations for a short 37 years.[4] Diseases introduced by French explorers and missionaries devastated the Neutral Confederacy, allowing it to fall victim to invasion by the Haudenosaunee around 1650. The Jesuits in Quebec City wrote that the Neutral Confederacy was driven from the area by 1653, with remnants of the once powerful group reportedly migrating to seek shelter with the Anishinabe nations on Lake Huron and Lake Superior.

Following the war, the area around Waterdown was sparsely inhabited by newly arrived Haudenosaunee. The Haudenosaunee village of Tinawatawa (alternatively spelled Quinaouatoua) was located near to Waterdown, likely somewhere along the upper course of Grindstone Creek, and was one of only a few villages established in the newly conquered territories. Following the upheaval of the so-called Beaver Wars the Haudenosaunee abandoned their settlements north of Lake Ontario, and the Anishinabe people moved into the region.

1669 saw French explorer Robert de la Salle follow Spencer Creek (from Lake Ontario) up toward present-day Westover and the native settlement of Tinawatawa. It was here that la Salle met up with another French explorer, M. Louis Joilet. Some historians think this meeting happened along the shores of Lake Medad (northeast of present-day Waterdown, beside Hidden Lake Golf Club).[5]

After the fall of New France the region changed dramatically. The Anishinabe forged an alliance with the British Crown that was reaffirmed by King George III's Royal Proclamation of 1763. Politically, the region became part of the Province of Quebec that was created by the British.

The area remained largely unaffected until the American Revolution unleashed a flood of Loyalists fleeing the American republic. Access was largely restricted to water, so the first settlements were along the coast of Lake Ontario. To facilitate the English-speaking settlers, the Province of Quebec was broken into Upper and Lower Canada with Lieutenant Governor John Graves Simcoe as the first representative of the Crown for Upper Canada. It was John Graves Simcoe that was walking along the beach strip of Hamilton that looked up at the escarpment and named its northern arm around Burlington Bay "Flamborough" because it reminded him of Flamborough Head in Yorkshire, England.

The Flamborough area was ceded to the Crown by treaty with the Anishinabeg on May 22, 1784. The frontline of the new township was laid out by John Collins in 1790 with further surveys conducted through to 1797. Originally meant to be the Township of Flamborough, it was broken into the separate entities of East Flamborough and West Flamborough in 1798. Today Waterdown is the largest settlement in the former township of East Flamborough.[6]

One of the first land grants in the area was to Lt. Alexander MacDonell of Butler's Rangers. MacDonell never visited the area, but ended up selling 800 acres to Alexander Brown of the North West Fur Company in 1802. Brown built a log cabin and sawmill at the top of the Great Falls in present-day Smokey Hollow in 1805, making him the first European settler in the region. Alexander Brown married Merren Grierson and was a key figure in the community until his death in 1852. Eventually moving down Grindstone Creek to the site of present-day LaSalle Park, Brown built a wharf (called "Brown's Wharf" or "Port Flamboro") to export the many things being created by the mills that quickly sprung up in the Waterdow-area.[7] It was Alexander Brown that built the first school of the village (on the site of the present-day American House) in 1815, employing Mary Hopkins as its first teacher.

Waterdown's fire department is station 24 of the Hamilton fire department.

It was the arrival of entrepreneur Ebenezer Culver Griffin in 1823, purchasing over half of Alexander Brown's property, that marked the true beginning of the Village of Waterdown. It was Griffin that had his property surveyed into village lots in 1830.

A local story credits Ebenezer Griffin with giving Waterdown its name. A prohibitionist, Griffin did not approve of the vast quantities of alcohol being consumed during the Victorian Age, including the whiskey used to christened new mills. During the christening of one of Griffin's mills the carpenter called out for its name and someone in the crowd called out "Hey Ebenezer, throw that water down." The carpenter heard the name "Waterdown" and it was given to the mill and soon adopted by the emerging village.[8] It is important to note that Alexander Brown did not share Griffin's displeasure of alcohol.

Waterdown was born out of the Industrial Revolution. Thanks to the plan drawn up by Ebenezer Griffin, settlers and industrialists rooted themselves in village life. Mills grew along the banks of Grindstone Creek (especially in the area known as Smokey Hollow - given this name because of all the smog caused by the many complexes) as individuals like William P. Howland arrived to make their fortune. By 1879 the settlement was severed from the Township of East Flamborough and incorporated as a Village in its own right with quarrier Charles Sealey as its first reeve. Waterdown remained its own municipality until it was absorbed into the Township of Flamborough in 1974.

Ontario's Conservative Ontario embarked on a province-wide restructuring on municipal government, amalgamating several municipalities into larger ones. The Regional Municipality of Hamilton–Wentworth was no exception, and it was proposed that the six municipalities, including the Town of Flamborough, be merged into an amalgamated City of Hamilton. Many Waterdown residents disagreed with this proposal. Due to Waterdown's location as a sandwich town, resting between Burlington and Hamilton, residents argued that Hamilton would not extend city services, such as bus routes, to Waterdown. Instead, they suggested that Flamborough be split into parts, with Waterdown amalgamating with Burlington.[citation needed] Burlington had expressed some interest in amalgamation and there was support for this idea in Waterdown. Burlington is closer geographically and the Aldershot and Kerncliff Park neighbourhoods wrap around the south and east ends of the community. Burlington had also expressed a willingness to expand bus service to Waterdown.

However, despite a local campaign to sway the government, Waterdown was amalgamated into Hamilton with the rest of Flamborough. This prompted the elected MPP at the time, Conservative Toni Skarica, to resign from his position. Skarica ran (and won) partially due to a platform of keeping Flamborough unamalgamated, and vowed to resign if the government forced an amalgamation with Hamilton. He gained a brief local celebrity status during that time because of his stance.