Once Agnes had completed her time at the Normal School in Stratford, she applied to five teaching positions and got them all. Ultimately, she chose to teach at Gowanlock's school, six kilometres from Port Elgin. Her first year of teaching was exhilarating and she made quite a positive impression on the community. However, Agnes naively followed the advice of an instructor in Stratford who told his charges that proper conduct required one to resign at the end of their first year so that the board could assess their performance. The board chose not to reassign her, not because they were unhappy with her work but because they believed that her resignation meant that she was dissatisfied.

Although this was certainly unfortunate, if it were not for her next position - which she easily found at Kinloss - Agnes may have never found her political passion for agrarian issues. While teaching in Kinloss, Agnes boarded with the Bradens, a couple who owned a typical country general store where local farmers would frequently gather to shop and socialize. Both Agnes and Sam Braden were devout Liberals and wouldn't hesitate to take part in political with vocal Conservative customers.

However, Agnes was forced to take a year off due to issues with her mental health during her third year of teaching. During this time, she had ample time to think about her life.When she had recovered, Macphail taught in Alberta where she came into contact with an organized farmer's movement for the first time.

Unimpressed by the Albertan weather, she cut short her stay and returned to teach in south western Ontario. This was when her teaching methods became even less conventional as she rebelled against the school system's emphasis on exam preparation. She got the board to purchase magazine and daily paper subscriptions, and her class would pick an element of the news to focus on. Agnes also gave the older students the books of Nellie McClung so that they could discuss reformist and feminist ideas.

Her teaching career lasted a total of ten years.