It was the first of 24 gold medals up for grabs on Wednesday as the Paralympics got underway.
Medals were also contested in swimming and wheelchair fencing on Wednesday.
Greco was born with cerebral palsy, which mostly affects the right side of her body. It was her first Paralympic Games medal, winning her race in 3 minutes, 50.815 seconds.
“It feels amazing,” Greco said. “I still can’t believe it. I keep looking down and seeing (the gold medal). It’s not really sunk in yet.”
Wang Xiaomei of China was second and bronze went to Denise Schindler of Germany.
Greco took up cycling just over three years ago after competing in track and field for seven years.
Australian teammate William Martin also won gold in the first swimming final of the Paralympics, taking the 400-meter freestyle in the S9 class in 4:10.25 seconds. Ugo Didier of France took silver and Alex Tuckfield of Australia won bronze.
In the first wheelchair fencing final, Li Hao of China won gold in the men’s individual saber. He defeated Artem Manko of Ukraine 15-12 in the final.
Away from the competition, International Paralympic Committee (IPC) spokesman Craig Spence confirmed the IPC is in contact with two Paralympic athletes from Afghanistan who have left the country. He declined to speculate whether they might eventually reach Tokyo for the Paralympics.
“There’s a lot of speculation going on where these Afghan athletes are,” Spence said. “I’m not going to tell you where they are because this isn’t about sport, this is about human rights and keeping people safe.”
He added they were in a “safe place.”
Several reports say the two athletes—Hossain Rosouli and Zakia Khudadadi—may have arrived in Australia.