The team was founded in 2020 with their inaugural regular season held in Lake Placid, New York, followed by the Isobel Cup playoffs in Brighton, Massachusetts.

[7] The team's ownership was announced as a group of Boston-based investors headed by Johanna Neilson Boynton, a former competitor with the Harvard Crimson women's ice hockey program.

The team simultaneously announced its first five signed players as Kristen Barbara, Elaine Chuli, Shiann Darkangelo, Emma Greco, and Taylor Woods.

The team announced Mandy Cronin, CWHL co-founder and former goaltender of the Buffalo Beauts, as general manager on May 11, 2020.

[19] Due to the ongoing restrictions during the COVID-19 pandemic, the Six started their inaugural season in a bubble with the rest of the league in Lake Placid, New York, in January 2021.

[21] The following day, Lindsay Eastwood scored the first goal in franchise history via a power play in an eventual 6–5 shootout loss to the Minnesota Whitecaps with assists credited to Emma Woods and Shiann Darkangelo.

In May 2021, the owners of the Six also bought the Metropolitan Riveters as part of the league's push to have all teams be independently owned.

The Six added Hockey Hall of Fame member Angela James to their coaching staff on June 24.

Picking third overall, the Six selected Maegan Beres from Boston College, followed by Tatum Skaggs fourth overall, and York Lions skater Taylor Davison with the fifth pick, marking the second straight season that the Six have drafted a player from a U Sports women's ice hockey program.

[36] Towards the end of the 2021–22 season, the team was sold to a new ownership group including Anthony Stewart, Angela James, Bernice Carnegie, and Ted Nolan.

[42] On March 26, 2023, the team won the Isobel Cup Championship, defeating the Minnesota Whitecaps 4–3 in overtime at the Mullett Arena in Tempe, Arizona.

[43] After the season, it was announced that the PHF had been purchased as part of a bid to create a new, unified professional women's league.