In 1854, with the construction of the Great Western Railway line through Hamilton, and the call for a downtown station, a number of spirited citizens felt that the city was lacking a first-class hotel. A joint stock company was formed and public subscriptions canvassed to raise enough money to build the kind of hotel that would reflect the progress of the "ambitious city". When the hotel was constructed, the building cost was estimated at $100, 000. The Anglo American Hotel stood five stories high and had extensive front and rear grounds. The hotel had over 150 rooms, magnificent parlors and bathrooms, a bar and billiard rooms. The lower level of the hotel appeared to be destined for shops. The Anglo American Hotel hosted the Prince of Wales for the city’s first Royal Visit in 1860. The building proved too large for the city it was intended to serve and before long it was seen that such a fine and expensive hotel would have difficulty in paying its way. As Butler pointed out: "the Anglo American was built before the time it was needed" (Spectator, December 2, 1989).

The Methodists bought the building for $24, 000 with the intention of transforming the building into a ladies’ college that was given the name The Wesleyan Female College which was later changed to the Wesleyan Ladies’ College. The presence of the college was of great educational and historic significance. At this point in history, girls were rarely given any form of formal education. Many had to fight to simply learn to read and write. Even the education of wealthy female children was substandard, consisting of a curriculum of Singing, Dancing, Graces of polite society, and basic Art and Literature. The creation of a ladies’ college in Hamilton, whose primary function served for the education of young women, was groundbreaking.

There was a female college in Dundas, built in 1830, on the north east corner of Ogilvie Street and Hatt Street that had the same name as the Hamilton college. The Dundas school had went by two names: The Dundas Female College and The Wesleyan Female College. It was fostered by the Wesleyan Methodists of Canada. The school opened in 1858. In 1861, Rev. Samuel Dwight Rice founded the Hamilton College. In February 1866, the Wesleyans decided to combine the two institutions whose location was to be in Hamilton.

The Hamilton branch of the Wesleyan Ladies’ College officially opened in September of 1861, drawing students from all parts of Canada and the United States. Its foundation was largely due to the efforts of Mr. Edward Jackson (one of the most enterprising citizens of Hamilton), Dennis Moore and Mr. Joseph Lister. The faculty was composed of the finest teachers the country afforded, including teachers hired from Europe to teach modern languages and music. The first principals of the school were Rev. Alexander Burns, D.D., L.L.D and Rev. Dr. Samuel Dwight Rice.

The facilities of the college were exquisite. According to Mr. Burns: "No other college in the Dominion contains such halls, bedrooms, recitation rooms and parlors, nor so fine a dining room." The college housed both boarding and day students, from all religions and backgrounds. "While the name of the College is denominational, its doors are open to all; and its graduates and pupils belong to all religions. Higher education of young ladies is the sole aim of the institution . . . culture in all that is beautiful and useful is one aim of the college, and the highest praise for its performance of its work is none too good". The principles of the school stressed: "Truthfulness in opposition to pretense in anything, patriotism, love of home, devotion to parents, simplicity, inartificiality, avoidance of heartlessness and display" while the aim of the school sought "to produce a rich, deep and graceful character, generous and sympathetic, with self-reliant independence of   thought and freedom from weak sentimentalism."

The academic curriculum consisted of traditional subject matter (Reading, Writing, Arithmetic,History, Geography, Science, and English) as well as other interesting fields of study (Modern Languages, Classics, Anatomy, Physiology, Geology, Natural Theology, Logic, Moral Philosophy, Drawing, Painting, Music, Zoology, Botany, and Wax Fruit and Flower Arrangement). The school also had a renowned literary society, a conservatory of music, a cooking school, and a newspaper that went by the name "the Portfolio". During the career of the College, over two thousand women were educated and there were over two hundred graduates. Of the graduates of the class of 1888, some of them obtained honours in the first Bachelor of Arts Degree, ever won by women in the province.