After becoming the first Swedish player to be named European No 1 in 2008, Karlsson was sidelined for four months last year suffering from blurred vision caused by fluid behind the retina in his left eye.
However, at Doha Golf Club the 40-year-old rekindled the form which saw him win twice in 2008 to ensure a second successive Ryder Cup appearance.
Karlsson produced the round of the week to win with a stylish bogey-free seven-under-par final 18 holes.
"The focus this year was to come back and start to put together a string of good rounds and then you never know what's going to happen," said Karlsson, following his 10th career title.
"It's not really the win, it's fantastic to win, but to play four really good rounds together, that's the most satisfying."
Karlsson had produced hints he was returning to form at the end of last year after losing in a play-off in Japan before claiming a second-placed finish alongside Henrik Stenson at the World Cup in China. "It has surprised me a little bit," he added. "Especially the way I played during the final round."
After beginning the day two shots adrift, Karlsson shared a one-shot lead with Bradley Dredge at the turn, but as the Welshman's challenge faltered, Lee Westwood mounted a late bid with a run of four birdies in five holes.
The European No 1 and world No 4 trailed his playing partner by one shot with four holes to play, but was becoming increasingly frustrated with a new driver after cracking the face of his previous club during the third round.
Westwood's challenge, however, came to an abrupt halt with a three-putt bogey with two holes remaining before Karlsson ensured his first victory since the 2008 Alfred Dunhill Links Championship with back-to-back birdies. The big-hitting Spaniard Alvaro Quiros took advantage of Westwood's demise with a hat-trick of late birdies to claim second in an admirable title defence.
He said: " I chipped in two times and holed a very long putt in my final round so I have to be thankful."
Westwood was forced to settle for a tie for third a further shot off the pace alongside Australia's Brett Rumford (69) after a final round 70 handed him a 12th top-10 finish from his last 15 outings.
"It's hard to imagine anything else going wrong this week, so 11 under is an unbelievable score," said Westwood. "I had to play virtually all the back nine with a three wood. You can't play this course out of the rough and when I pulled the driver out it went in the left rough. And it is tough to play it with a three wood because it's such a long course. Long, straight driving is one of my strengths and if you take someone's strengths away from them it is going to very difficult to compete."
Oliver Wilson recovered from being involved in a minor car crash on the way to the course to card a one under 71 to claim fifth at eight-under-par alongside joint overnight leaders Dredge (74) and Paul Casey (74).
Scotland's Marc Warren finished in a tie for 20th on four-under after a closing 74 – his worst round of the week – with Richie Ramsay (70) tying for 32nd and Stephen Gallacher (75) just creeping inside the top 50.