In late 1924, Dr. Polyvios Korrylos, a well-known surgeon and professor at Cornell University came to Chicago with the intention of organizing a professional society. He went to visit Dr. Nikolaos Salopoulos, who was the first Greek Consul in Chicago. The two discussed several ideas, before coming up with names of fifty individuals with whom they would present their idea. Salopoulos invited all fifty to a dinner at the LaSalle Hotel and explained the vision to them. The Greek Professional Men's Club was formed that very evening, with Salopoulos elected as honorary president.

The first formal meeting was held in the spring of 1925, and 30 people attended. Dr. Sotirios Zaph was elected the first working president. The club was comprised of primarily doctors and most had emigrated from Greece.

The Greek Professional Men's Club began hosting lectures that year, many of which were very controversial in nature, stimulating debates questioning history, taking on sensitive political topics and the like. Much controversy surrounded the organization, over the years, not only due the nature of its lecture topics, but also from in fighting, power struggles and a lack of funding that threatened to stifle the growing club. The intellectual and cultural stimulation that was created would prove to be the glue that has held the organization together, to this day.

Women were prohibited from joining, and a few years after the Men's Club's founding, the Greek Women's University Club was formed to provide Greek women with a professional forum.

A few years later, social events were added to the calendar, bringing Hellenic professionals together to celebrate national holidays and religious events. These events presented a more casual environment in which Hellenic professionals could meet and exchange ideas. Social events have remained at the core of HPSI's calendar of events.

One of the first programs instituted was to honor college graduates of Hellenic descent. A scholarship program was established in conjunction, as an impetus to continuing education. Graduates were honored, mentored and deserving students were awarded scholarships in what has become an HPSI tradition.

As more Greeks went to college and took up professional careers, the make up of the organization changed, with lawyers, professors and other professionals joining the ranks.

In the late 1940s, there was some talk about approving women into the membership. It wasn't until 1954, when then-president Gus Mazarakis made the historic decision to allow women to join their male colleagues. The name was then officially changed to the Hellenic Professional Society of Illinois.

It would be another 25 years before the Society would elect a woman president. Angelique Sallas, PhD. was elected to the presidency in 1975. Ironically, she is the grandniece of founding father Salopoulos.