The USA looked headed for more disappointment against their arch rivals when trailing late in the third period, but captain Hilary Knight tied it to take the Games decider to three-on-three sudden death hockey, where Keller went around defender Claire Thompson and slipped the puck past the Canadian goalie to clinch a third Olympic gold for the US women.
The game at Santa Giulia Arena gave fans yet another classic chapter in the sport's greatest rivalry, and the packed stands offered duelling chants of 'Canada!' and 'USA!' from puck drop.
The Americans were the favourites after handing Canada their first-ever Olympic shutout 5-0 in the group stage, but fears of a one-sided final were soon dispelled as the Canadian goalie Ann-Renee Desbiens put on a lights-out performance through the first period.
The USA had a prime chance to break the impasse with a power play at the start of the second. Instead, the crafty Canadian squad flexed their muscle as Laura Stacey gathered the puck in the neutral zone, charged forward and sent it across for Kristin O'Neill, who made a nifty backhand move to score the shorthanded goal.
Finding themselves behind for the first time in the tournament, the US could not find a way past Desbiens until they pulled their goalie for an extra skater with just over two minutes left in regulation.
Knight redirected a shot from Olympic rookie Laila Edwards for their desperation first goal, breaking the all-time US women's goals record at the Winter Olympics in the process.
"She's been a part of every historic moment since she's been a part of this team. For her to get that goal was obviously most important for our team, but also just a huge honour for her to break that record," said Kelly Pannek, Knight's teammate on their 2018 gold medal-winning group.
"It's something we all want for her."
This was the third time in the last four Games that the two sides have battled into overtime in an Olympic final, and the crowd held its breath before Keller finished off the Canadians with just over four minutes gone in overtime.
"Everything happened fast," Desbiens said of the score that just squeaked over the line. "I'll see that one for a long time."
US goalie Aerin Frankel also proved up to the test, ultimately turning aside 30 of 31 shots the Canadians sent her way.
With their coach, John Wroblewski, weeping tears of joy behind the bench, the American team erupted in celebration, and the Canadian side could only stand by grimly ahead of the medal ceremony, as fans danced to Miley Cyrus' Party in the USA.
It marked the once-dominant Canadians' eighth successive loss to the Americans.
The Canadians had long had the upper hand on the United States, with five Olympic golds. But cracks in the ice beneath their feet were beginning to show before they even stepped into the rink in Milan.
The United States won the world championship last year before sweeping the Canadians in the four-game Rivalry Series in November and December, leaving Canada fans with a queasy feeling just weeks before the Games were set to begin.
As American youth triumphed over Canadian experience on Thursday, US fans can allow themselves to dream of more hardware to come, with several collegiate players on the team having yet to reach the professional ranks.
The USA were playing in their seventh Olympic championship game, having missed just one since the women were added to the Games' programme in 1998. Switzerland took the bronze medal earlier on Thursday with a 2-1 overtime win over Sweden.