Jorgensen pulled ahead in the run leg and finished with a time 1 hour, 58 minutes, 38 seconds. Japan's Ai Ueda was second with a time of 1:59.14 followed by Agnieszka Jerzyk of Poland in 1:59.24.
Jorgensen took the lead from Ueda on the second of four laps and held on for her first win of the season. Ueda became the second Japanese athlete to podium at Yokohama, alongside Juri Ide, and claimed her first career medal.
Britain's Jodie Stimpson, who won the first two events of the season, finished ninth despite suffering a cut foot and maintained her lead in the overall standings after three rounds.
Javier Gomez of Spain won the men's event, clocking a time of 1:45.31 to edge compatriot Mario Mola in a photo-finish. Richard Murray of South Africa was third with a time of 1:46.00.
Alistair Brownlee of Britain finished fourth while his brother Jonathan was fifth.