The Boels Dolmans rider finished ahead of team-mate Megan Guarnier and Jolanda Neff (Servetto Footon) after attacking late in the 123.3km race from Gavirate to Cittiglio.
Armitstead responded to an Neff at the front of the race before launching a decisive on the young Swiss mountain biker with 3km to go.
“I had in my ear our director telling me it wasn’t our responsibility to chase,” Armitstead said.
“He said to stay calm and wait, but I was a little frustrated because I knew the peloton was not that far behind us. [Giorgia] Bronzini was still there.
"She was riding really strong today, and, of course, in her home WorldTour race, she’s going to be motivated. I didn’t want the peloton coming back.
“I did a little more work than what I was told to do on the radio. On the final climb, Rabobank attacked, and because I had done a lot of work to keep the break going, I was dropped. I could see them, and I knew I had to come back.
“I came directly back on the top of the climb. I attacked directly. It was my last move. Today we were working for Megan, and I was just being a teammate and doing a stupid attack. But nobody saw me coming from behind, and I had a lot of speed.
“I jumped. I was sprinting for the line, and Neff couldn’t match my speed.”