The 46-year-old, who succeeded his father Keith as chairman in 2011, has made the decision on medical advice.
"I have greatly enjoyed my time being chairman of this great club, and this is a decision that has not been taken lightly," said Barwell.
"A lot of thought has gone into the decision, along with lengthy discussions with my family. I believe that the time is right for me to step aside, safe in the knowledge that we are on the right track, on and off the pitch."
He added: "With six finals in six seasons, and the club continuing its good financial performance, the Saints are certainly heading in the right direction. I trust the board in making the right decision as to who the new chairman will be, and I will be giving him or her my total support."
During Barwell's tenure the club reached Premiership and LV= Cup finals, and he will remain on the board along with his father Keith and sister Ella.
The Barwell family will also maintain their majority shareholding of the club, while vice-chairman Tony Hewitt takes over as acting chairman while the board go through the process of finding a new chairman.
- Sports & Recreation