The 23-year-old American - 16th at the Tokyo Olympics - entered the second leg of the race with a 34-second advantage over her rivals and managed to grow her lead to an incredible 2 minutes and 44 seconds by the end of the 40km bike.
Knibb eventually crossed the line with a time of 1:54:47, giving her not only her third win of her career but also propelling her to second place in the final rankings for the season.
With a lead of 667 points heading into the final race, Bermuda's Olympic champion Flora Duffy finished in third place - more than enough to earn herself a third world title and with it a slice of history, becoming the first triathlete ever to win an Olympic gold and become world champion in the same year.
The 33-year-old now boasts an impressive 10 titles during her distinguished career, with the Olympic gold and three world titles adding to Commonwealth gold and five world titles in other racing formats.
World Triathlon Championship Series, Edmonton - Final Leaderboard
1. Taylor Knibb (USA) - 1:54:47
2. Leonie Periault (FRA) - 1:55:43 (+0:56)
3. Flora Duffy (BER) - 1:56:11 (+1:24)
4. Katie Zaferes (USA) - 1:56:14 (+1:27)
5. Taylor Spivey (USA) - 1:56:16 (+1:29)
6. Maya Kingma (NED) - 1:56:23 (+1:36)
7. Sophie Coldwell (GBR) - 1:56:46 (+1:59)
8. Laura Lindemann (GER) - 1:56:56 (+2:09)
9. Vicky Holland (GBR) - 1:57:32 (+2:46)
10. Kirsten Kasper (USA) - 1:57:47 (+3.00) body check tags ::