Radford was neck-and-neck with Ryan during the men's race but overtook him in the last straight to win by seven seconds in a time of 37 minutes 9 seconds.
"That was the goal to come here and take it out, especially with it being in my hometown," he said. "This is the first time we have been able to hold an event like this and to be able to come out with the win is really good."
Radford, Ryan and Webby will all head to Portugal in Juneaiming to qualify for the Rio Olympics in the 10km open water swim event. They have to finish in the top nine at the final qualification event in Portugal to make the cut.
To help simulate the open water swim at the Olympics, Radford decided to compete without a wetsuit in Blue Lake.
"It's something that I look as kind of putting a handicap on myself, to make myself work harder.
"I don't want to be out there swimming in my comfort zone as such. I've come here to really push myself and I really achieved that today by not having a wetsuit on."
Gillespie was rapt to win the women's title, backing up from her round-four win in Christchurch.
"I'm always happy with a win, but it was very tight today," she said. "We were pretty much even from the beginning so the pressure was on right from the start."
The front three in the women's race all finished within 11 seconds.
]"I knew that from the last buoy I had to consistently pick up the pace and managed to hold on," Gillespie said.
Results:
Men: 1 Kane Radford (Rotorua) 37:09; 2 Phillip Ryan (Auckland) 37:16; 3 Liam Thomson (Australia) 38:07.
Women: 1 Stefannie Gillespie (Dunedin) 40:07; 2 Charlotte Webby (New Plymouth) 40:10; 3 Claudia Ashby (Hamilton) 40:18.