Stumbling out of the blocks, Karlsson bogeyed three of his first four holes and saw his two-shot lead over Emanuele Canonica all but disappear.
Playing in the shadows of the Swiss Alps, the 6-foot-5 Swede then proceeded to cast his own shadow over the field as he strung together five birdies through the middle of his round.
His four closest pursuers all but imploded as they combined to shoot 11-over-par for the day and watched as Karlsson notched his first win of the season.
Robert Karlsson talks about his win.
Scotland's Paul Lawrie and South African Trevor Immelman both carded 1-over-par 72s and finished four back of winner, and in a tie for second place.
Lawrie, whose recent victory at the Wales Open had him poised to challenge the leader, couldn't mount much of a charge and ended his day with bogeys on three of his last five holes.
Immelman, who was 3-over-par through 13, also didn't put any heat on Karlsson, but was able to garner his third second-place finish of the season. He also can take comfort in the fact that he was the low South African, no small feat considering that the world's No. 3 and 4 ranked players, Ernie Els and Retief Goosen, were in the field.
Bradley Dredge and Simon Dyson shot 67 and 68 respectively for a 9-under four-day total and good for a share of third place.
Canonica, paired in the final group with Karlsson, took himself out of contention by bogeying the eighth, ninth and the 11th, then watched as Karlsson chipped in for birdie at the 13th. His final round 75 put him in a tie for sixth.
Karlsson's wire-to-wire victory was worth a $147,076 and was his first since last year's Via Digital Open de Espana.
Full-field scores from Omega European Masters