Isaako scored a hat-trick of tries and converted 13 of New Zealand's 14 tries in a lopsided Group A match in Christchurch.
It was the first win of the tournament for the Kiwis, who opened with a 24-22 loss to defending champions Australia while the Cook Islands crashed to a second heavy defeat.
The Kukis scored three early tries, all through winger Esom Ioka, to surprisingly lead 16-12 after the opening 20 minutes.
However it was one-way traffic from that point, with New Zealand pulling 36-16 clear by halftime, slicing through with increasing ease against a defence that became frayed as the match wore on.
There were try-scoring doubles for Kiwi backs Ronaldo Mulitalo and Casey McLean, along with forward Tanner Stowers-Smith, who was on Test debut.
Isaako's haul was the second most by a player in a World Cup match, eclipsed by Ryan Girdler's 46 points for Australia in their 110-4 defeat of Russia in 2000.
Kiwi captain James Fisher-Harris said the opening exchanges were tough.
"The Kuki brothers came with that aggression and obviously put some points on the board but we just stuck to what we do best. At the end of it, it was pretty fun," he said.
Cook Islands skipper Kayal Iro said his team struggled to contain opponents stacked with top-flight players from the National Rugby League competition.
"They were just too good for us. I thought we came out hard and obviously Esom had a blinder, but we just couldn't really hold on."
Australia and Fiji, who were first-up winners in Group A, were to meet in Brisbane later on Sunday night.
The group concludes next week when New Zealand face Fiji on the Gold Coast and Australia play the Cook Islands in Townsville, with the top two ranked teams advancing to the semi-finals of the 10-team tournament.