Before colonization, the area was deliberated by the surrounding indigenous communities to be a "neutral" zone.
Around 1827 Guelph was picked as the
headquarters of British development firm "the Canada Company" by its first superintendent John Galt, a popular Scottish novelist
.
Galt designed the town to mirror a European city center, complete with squares, broad main streets and narrow side streets, resulting in a variety of block sizes and shapes which are still in place today.

The town was named to glory Britain's royal family, the Hanoverians, who were descended from the Guelfs, the ancestral family of George IV, the reigning British monarch.

The first cable TV system in North America was in Guelph. The first broadcast was in 1953.