The Swiss started the free technique event just 13.5 seconds ahead of main rival Petter Northug but had extended that advantage to over a minute inside 7km and came home in 1:09:25.2
The 15 bonus seconds for the victory means the 25-year-old Olympic 15km champion will start Saturday's penultimate stage, the 20km mass start, with a commanding 1:20.8 advantage.
Current World Cup leader Northug had relinquished the 75-second lead he held over third placed Russian Alexander Legkov inside the opening quarter and by the 20km point had been joined by Devon Kershaw, Maurice Manificat and Marcus Hellner.
Northug regrouped to win the sprint for second, crossing 1:15.8 behind the winner but losing a further five bonus seconds to the Swiss.
“I was a little bit surprise when Petter Northug dropped but I felt very good and it was a perfect race for me,” said Cologna.
“It was very tough, especially the last part but I am happy with the advantage. We will have to see what happens - it is not decided yet. The 20km is left and that will be some hard racing with lots of bonus seconds there.”
Legkov beat out Canada's Kershaw for third place and the final five bonus seconds while Sweden's Hellner and Manificat of France followed close behind to boost their chances of a podium place in the overall.
The nine-stage, 11-day event finishes on Sunday with the 9km stage concluding with the climb to Val di Fiemme.