The Englishman accelerated away from the favourites group with Chris Froome (Team Sky) and Tom Dumoulin (Team Sunweb), and joined his team-mate Esteban Chaves who had been in the all-day 28-man move. Together they rode to victory: Chaves the stage, Yates taking the overall leader's pink jersey from Rohan Dennis (BMC Racing).
"In the end it was a really a perfect day," Yates said wearing the famous maglia rosa.
"It wasn't really the plan for Esteban to go in the breakaway, but it was very crazy in the start, a lot of guys went up the road and he just happened to be there. In the final, I saw a moment there where I had a small gap. We tried."
Yates saw the moment in the final of the 15-kilometre climb up the cold and misty Mount Etna. At 1.5km out, he rocketed away from 2017 race winner Dumoulin, Froome and other favourites.
"I had good legs and I felt really good. I didn't have to do anything because Esteban was up the road. I could sit in the wheels and save some energy," Yates continued.
"I just saw a bit of a moment where we'd been riding quite hard for a little bit and I had a very small gap. I thought OK, this is my moment."
Watch: Giro d'Italia stage six highlights
"We worked well, not just today but from the start of the season," Chaves added. "Good work from start of season, but today was special, to win on Etna. It's a dream to have the stage, pink jersey and blue jersey. When Simon Yates caught me he said, come on, let's go, let's go, you take the stage today.
"Today was fantastic but it's only one day. We'll hope to continue in this way. Tomorrow won't be easy after the long transfer after the stage we'll see in the longer climbs."
The race continues on mainland Italy after it transfers from Sicily tonight. With six stages down, Yates has 15 left if he wants to win the race overall in his first participation of the Giro d'Italia.
"I have a little bit of experience of holding a leader's jersey already. Hopefully that can help me in the next few stages," Yates explained.
"I don't know, I hope so but there are a lot of stages to go. Strong team, we can defend for a long time. To take it all the way to Rome will be difficult."
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