Nesbitt, from London, Ont., who won the 1,500 World Cup title on Saturday, claimed the last 1,000 race of the season in one minute 15.04 seconds, with Heather Richardson of the United States second, 0.73 seconds behind.
Zhang Hong of China was third, 0.79 seconds behind Nesbitt, who tops the standings with 550 points, ahead of Richardson on 459.
Nesbitt also broke the six-year-old track record at Berlin's Sportforum of 1:15.17 set by German skater Anni Friesinger.
"It was nice to beat Anni's track record because she's been so dominant for so many years," said Nesbitt. "Even though she's been retired for two seasons she still has left a legacy behind. It's nice that I know that I've gone faster than she's ever gone here, which is pretty special for me."
Nesbitt claims the Grand World Cup and its US$20,000 prize for the season's best skater after establishing an insurmountable lead over Martina Sablikova of the Czech Republic and Dutch skater Ireen Wust, who did not compete in Berlin due to illness.
"It was pretty exciting," said Nesbitt. "We did award ceremonies for the last hour and a half. But I know I have to go back and relax and not spend so much energy, because worlds are just in two weeks."
Canada also won gold in the women's team pursuit ahead of second-place Korea and Russia in third. Nesbitt joined Winnipeg natives Cindy Klassen and Brittany Schussler to win their third gold of the season in 3:01.03. The win captured the season title for the team.
"I think we had a pretty good race," said Nesbitt. "I was pretty tired because I had just raced 30 minutes before. Cindy was pretty worried, but she ended up being the stronger one of the three of us. We've been flexible with our tactics. We know how to skate well together."
Meanwhile, Dutch skater Kjeld Nuis claimed the men's Grand World Cup while Olympic champion and world record holder Shani Davis of the United States won the men's 1,000 in 1:09.24 to clinch the overall title.
Davis finished 0.12 seconds ahead of Nuis and 0.13 seconds ahead of Mo Tae-bum of South Korea, and ends the season 20 points ahead of Stefan Groothuis of the Netherlands, who could only manage fourth in the last race of the season.
Nuis finished the season with 84 points, ahead of Groothuis on 81.5 and Davis on 80.
Denny Morrison of Fort St. John, B.C., and Edmonton's Jamie Gregg were fifth and sixth place, respectively.
Former Olympic champion Claudia Pechstein of Germany claimed victory in the women's 20,000-meter mass start, her first World Cup victory since a two-year ban for suspected blood doping.
Mariska Huisman of the Netherlands finished second, enough to take the overall title after three events, with Pechstein second and Austria's Anna Rokita third.
It was a similar story in the men's event, where Alexis Contin of France claimed the overall title after finishing second in the last race of the season behind Jorrit Bergsma of the Netherlands. The Dutch also claimed the men's team pursuit title.