Launched first by Remco Evenepoel then by the Dane Michael Morkov in the last kilometer, Jakobsen won in the sprint ahead of the Colombian Fernando Gaviria (Movistar) and the Spaniard Jon Aberasturi (Trek-Segafredo).
The Dutchman, European champion, thus won his first victory of the season, the 39th of his career.
In the general classification, the Irishman Sam Bennett (Bora-hansgrohe), 4th in the stage, remains in the lead after his victory on Sunday in the 1st stage. Jakobsen is 2nd at the same time as Bennett and Gaviria is 3rd at 4 seconds. For his part, Remco Evenepoel quietly finished the race in the peloton, without wasting time.
Tuesday, the third stage will reserve a relatively flat course for the riders over 170.9 km with a difficulty in the final around the Autodromo de Villicum. The 39th edition of the Tour de San Juan ends on Sunday with a 112 km stage around San Juan.
The Tour of San Juan returns to the calendar after a two-year hiatus due to the coronavirus. Remco Evenepoel won the last edition in 2020.