The 22-year-old carded a five under 67 to stand on top of the leaderboard alongside fellow Swede Alex Noren and South African Jaco Van Zyl.
Karlsson had four birdies on the way out to turn in 32 and added further gains at the tenth and 13th.
A double bogey at the 17th threatened to spoil his day, but he responded with a closing birdie.
“That was a great start to the tournament,” said Karlsson, playing only his second European Tour event.
“Ever since I qualified on Monday, Ive been trying to really enjoy this experience. Its hard not to smile.”
Qualifying School graduate Van Zyl had six birdies against just one dropped shot.
“It was good. Really tough conditions, very good golf course,” he said.
The better-known Robert Karlsson opened with a respectable 69, one shot off second place which is shared by Sweden’s Niklas Lemke, Englands John Parry, Italian Lorenzo Gagli and Spaniard Alfredo Garcia-Heredia on four under.
The prestigious tournament is being played at Bro Hof Slott near Stockholm and comes to a climax on Sunday.