After riding 121km to the finish in Siena's Piazza del Campo,Armitstead beat European Champion Katarzyna Niewiadoma (Rabo Liv Women Cycling Team) and Emma Johansson (Wiggle High5) to take the race for the second time for Boels-Dolmans.
"It's amazing to win the first UCI women's WorldTour event and this race is absolutely special," Armitstead said.
"After winning the Omloop last week, thankfully I'm not affected by the curse of the rainbow jersey. I managed to honour it again today."
While she may not be suffering a curse, Armitstead admits it is hard being world champion.
“It’s difficult coming to every race and being expected to win them all,” she said. “I had a couple of messages from friends and family saying: ‘You’ll win on Saturday. It will be a breeze.’ I won – but it wasn’t a breeze. And it wasn’t a breeze winning Nieuwsblad. It may have looked easy, but it wasn’t."
The world champion was not particularly targeting this race, team tactics just fell that way. Her team-mate Nikki Harris - current Great British cyclocross national champion - attacked on the third section and was eventually absorbed by the peloton with around 30kms to go, when the lead group numbered 40 riders.
Rabo-Liv's Anna van der Breggen and Kasia Niewiadoma deployed the two-punch attack with Armitstead countering both, pulling clear with Niewiadoma and Emma Johansson (Wiggle High5) at the 13km to go mark.
Niewiadoma drove the pace up the final climb, but Armitstead passed her with 100m to go.
Armistead now leads the the Women's World Tour.
Them's the Rules
Last year's protagonist and third place getter, Ashleigh Moolman-Pasio (Cervelo-Bigla) along with Giorgia Bronzini (Wiggle-High 5) and 13 other riders were disqualified under the UCI's revised train crossing rule. The rule was revised after Paris-Roubaix where a number of riders came dangerously close to collision with a train.
Moolman said she was not aware of the revised rules.
"We were just about to rejoin the front group and a train was coming so the booms were going down. It was just starting to go down and we rode across and got disqualified. We were 100 metres to the peloton and there were only two cars between us. What do you do in that situation? I had never been in that situation before. I had really good legs and think I could have been on the podium today but that’s cycling."