US skier Jessie Diggins won the bronze, her first medal of these Games after a disappointing start in the skiathlon and classic sprint earlier in the Olympics.
Karlsson and Andersson had also claimed gold and silver, respectively, in Saturday's skiathlon.
Their success continues a streak of Swedish domination in the sport at these Games after the Scandinavian country swept the podium in the women’s classic sprint earlier this week.
Karlsson finished 46.6 seconds ahead of Andersson in Thursday's interval-style 10km race, where skiers start 30 seconds apart.
The strongest racers were seeded in the middle of the race, and the battle for silver and bronze was much closer, with Andersson besting Diggins by a few seconds.
Skiers contended with warmer-than-ideal temperatures on Thursday, prompting officials to salt the course ahead of the event to keep the snow compact, which could have given a slight advantage to earlier starters.
Some racers even cut the sleeves and legs off their uniforms as temperatures reached around 7C.