The 23-year-old Polish rider finished fourth overall in 2013, 53 seconds behind winner Vincenzo Nibali. However, he was only one second away from moving past Alberto Contador to secure a place on the final podium.
After just 18.5km of this race, Kwiatkowski already has a 24-second advantage over Contador and much bigger margins on many of his pre-race rivals.
Movistar's excellent third place in the team time trial limited Nairo Quintana's losses to 18 seconds but Richie Porte (Team Sky) is 27 seconds behind. Bauke Mollema (Belkin) starts stage two with a 37-second handicap, Cadel Evans (BMC) is at 47 seconds and Michele Scarponi (Astana) is at a more distant 54 seconds.
Garmin-Sharp's poor performance left Dan Martin at 1:04, while Chris Horner (Lampre-Merida) faces an uphill task to pull back 53 seconds.
Kwiatkowski will wear the best young rider's white jersey during the second stage to Cascina, with teammate Mark Cavendish in the leader's blue jersey. Kwiatkowski could take that jersey on Saturday's first mountain stage.
"For sure we're going to have a glass of champagne to celebrate but we have to stay focused because the hardest part of the race is ahead of us," he warned Cyclingnews.
Get The Leadout Newsletter
The latest race content, interviews, features, reviews and expert buying guides, direct to your inbox!
"It was a stressful day but I believed in my teammates and we did a great ride, without any problems on the corners or anything."
Cavendish said that Martin did much of the work to secure victory for Omega Pharma-QuickStep, with Kwiatkowski also doing some turns.
The young Polish rider admitted he did some of the work on the front but revealed he was scared of getting dropped.
"I did some turns but whenever I went to the back of the line I was scared that just an extra tenth of a kilometre increase in the speed would have put me out the back," he told Cyclingnews.
"As you move up the line you recover but then you make another effort on the front and you suffer again. It was hard and I was stressed out. Fortunately it was worth it and we won. Now we have to think of the rest of the race."
Stephen is the most experienced member of the Cyclingnews team, having reported on professional cycling since 1994. He has been Head of News at Cyclingnews since 2022, before which he held the position of European editor since 2012 and previously worked for Reuters, Shift Active Media, and CyclingWeekly, among other publications.
