Their relationship first began before the events of 1685 when John spoke out against George Sibley after he had branded poor Isaac for fornicating with his lover Abigail Cooke.
When John returns in The Vow Isaac tries to convince him that the witches are real and they soon become allies and when Isaac is arrested after he is spelled by the witches John is the only one who stands up for him and tries to stop him from being executed in In Vain
Both are firstborn sons in the new world and born and raised in Salem, Massachusetts though it is unknown of how much interaction they had with each other prior to the events of 1685. John with the rest of Salem watched as Isaac and his lover where punished for fornication and Isaac was branded though John was the only one that spoke out against his assailant but was later sent to join the militia in the nine years war.
Throughout The Salem Series
Isaac and John are reunited in The Vow when Isaac witnesses his arrival and later informs Mary Sibley of his return. The next night at the tavern Isaac tries to convince the captain that witches are real and when he learns the following day that he is leaving Salem he takes him into the woods where they spy on the witches Sabbath but they are stumbled upon by the witches but escape and return to Salem before they are recognised.
In The Stone Child when John discovers what has become on the body of Giles Corey, he enlist his help to retrieve him from the crag and the pair bury him in Salem's graveyard.
In In Vain following Isaac been spelled by the witches and attacks the prostitutes at The Divining Rod John watches helplessly as he is arrested. John tries to convince Cotton to save Isaac as he believes he is being framed for being a witch but later Joins forces with Mary to save him. When the the magistrate decides to hang Isaac for witchcraft John defends Isaac and attacks the militia men trying to prevent them from taking him to the gallows.
In Our Own Private America as the Barker family are burnt at the stake for witchcraft Isaac questions where John had been as he was supposed to save the people of Salem.
In Departures when George Sibley is injured after their carriage crashes. Isaac returns to Salem and seeks out John but John tells him to leave him their and keep quiet as he deserves no help from either of them.
In Ashes Ashes Isaac with the rest of Salem witness John's trial and later that night convinces Mary to save him.