In 1879, Mayor William Northwood built a high Victorian house at the corner of William and Murray Streets. Years later, the home was purchased by T.H. Taylor who spent his last years in the home. After his death, students from Chatham Collegiate Institute boarded in the home.

In 1904, the Chatham Mineral Water Company was formed and they purchased the Northwood home. Construction of an addition began in 1901 and the facility opened the next year. The mineral baths were very popular and in 1905 the company decided to build a completely new facility on the site called Hotel Sanita. This new structure was designed by the local firm of J.L Wilson and Sons. For a brief spell the hotel and baths were extremely popular, until the mineral springs dried up. The facility continued to operate as a hotel until prohibition dealt a final blow to the business.

In 1924, due to a crowded Central School, the hotel was turned into the Chatham Vocational School. This institution taught both commercial and academic students. The school was active until it was closed in 1962.

In 1963 the abandoned Chatham Vocational School was offered for sale to the highest bidder. It was purchased for $37,500 by a group of citizens eager to establish an art centre in Chatham. By 1969, The Thames Theatre Association for the Arts was presenting live performances in the original 700-seat school theatre and the old gymnasium was being used as a gallery. Renovations to the gymnasium and the studio areas of the building began in 1975 and the Thames Art Gallery, National Exhibition Centre was born. The City of Chatham assumed the financial responsibility for the Gallery in 1980.

In 1988, the Chatham-Kent Museum relocated from the Milner Heritage House to the Chatham Cultural Centre. The Municipality of Chatham-Kent became the owner and operator of the Chatham Cultural Centre in the same year.