The 56-year-old Scot will join up with Brady as his new assistant manager following the completion of his notice period with Blackpool.
"I am really pleased to be rejoining the club and I am hoping to be able to help all departments move forward, but the initial focus will clearly be on the first-team," said Calderwood.
"I have learned a lot in the years since I was last at the club and hopefully I can put all of that experience to good use.
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"The situation here is similar to the situation I arrived in at Blackpool in working with a talented young manager.
"I have spoken with Jon Brady a number of times, that relationship will build quickly and I am really looking forward to working with him and the rest of the coaching staff.
"I would like to thank everyone at Blackpool. We enjoyed a fantastic eight or nine months and I wish everyone well going forward.
"I am really excited to be joining Northampton Town and I can't wait to get started."