The Glengormley man took the victory in the Olympic Stadium after setting a blistering pace from the start and leading throughout the race to post a time of 1:58:65, just one second outside his personal best.
Speaking after the race on Sunday, an emotional McKillop said the win was "unbelievable".
He said: "To be back in the Olympic Stadium is incredible, it doesn't get any better than this.
"London was where I found myself and the people here are so supportive - it's great to be back and hopefully I can continue on with this good form."
The 23-year-old, however, said he was disappointed his family were not able to be in the stadium to celebrate the victory with him.
The win comes just days after McKillop cemented his place as the best athlete in his class.
At the World Championships in France the runner won gold in both the 800m and 1,500m event.
The Anniversary Games are being held in London to mark one year since the Olympics took place in the UK capital.
Last year McKillop won gold in both the 800 and 1,500m events and was named as the male athlete who most embodied the Paralympic spirit throughout the Games.