In the inaugural race of the women's world tour, Armitstead (Boels-Dolmans) sped away from Katarzyna Niewiadoma (Rabo-Liv) and Emma Johansson (Wiggle-High5) after the trio built up a lead of around one minute on the chasing group.
Armitstead left Johansson in her wake at the top of the final climb to complete a second win in two weekends following her victory at Omloop Het Nieuwsblad last week.
"It’s amazing to win the first UCI women’s WorldTour event and this race is absolutely special,” said Armistead.
“After winning in Belgium last week, thankfully I’m not affected by the curse of the rainbow jersey. I managed to honour it again today.
"We’ve shared the work in the last 10km with my two breakaway companions and I pulled away on the climb. It worked out really well.”
Armitstead's win sees her become the first rider to lead the UCI women's world tour. The next race is the Ronde Van Drenthe in the Netherlands on March 12.
Lizzie Armitstead in action.
Image credit: AFP
Strade Bianche 2016: Siena to Siena, 121km
1. Lizzie Armitstead (GBr) Boels-Dolmans
2. Katarzyna Niewiadoma (Pol) Rabo-Liv at 3 secs
3. Emma Johansson (Swe) Wiggle-High5 at 13 secs
4. Elisa Longo Borghini (Ita) Wiggle-High5 at 1-04
5. Anna Van Der Breggen (Ned) Rabo-Liv at 1-07
6. Megan Guarnier (USA) Boels-Dolmans at same time
7. Annemiek Van Vleuten (Ned) Orica-AIS at 1-13
8. Claudia Lichtenberg (Ger) Lotto-Soudal at 1-17
9. Lauren Kitchen (Aus) Hitec at 1-21
10. Leah Kirchmann (Can) Giant-Alpecin at same time
14. Dani King (GB) Wiggle-High5 at 1-29
23. Nikki Harris (GB) Boels-Dolmans at 3-29