Yates first Briton to win Tirreno-Adriatico
Former Vuelta a Espana champion Yates, 28, ended the eight-day "Race of the Two Seas" 17 seconds ahead of 2018 Tour de France winner Geraint Thomas in second and 29 seconds ahead of Poland's Rafal Majka.
Yates originally took the overall leader's blue jersey of the 55-year-old race after clinching Friday's 202km fifth stage in Sarnano, central Italy.
He is expected to feature at the Giro d'Italia which begins on October 3 and said he was worried ahead of the final day of racing.
"I tried to do my best, I was nervous before because of the situation. I tried to finish off the work for the team. They've been fantastic all week and today it was up to me. Really happy I could pull it off," Yates said.
"We still have some weeks away before we start and until the end it's still a long time away. I hope to hold my form all the way," he added.
Local rider Filippo Ganna edged Belgium's Victor Campenaerts by 18 seconds in the 10.05km circuit against the clock in San Benedetto del Tronto on the Adriatic coast.