In 2009 he had two successive runner-up finishes in the early Gulf Swing as well as four further top ten finishes to secure a place at the Dubai World Championship presented by DP World.

Oosthuizen finished second at the 2010 Troph閑 Hassan II in Morocco and then finally sealed his first European Tour victory in the Open de Andaluc韆 de Golf in March 2010. This season continued to improve for Oosthuizen when he became the fourth man from South Africa to lift the Claret Jug when he won his first major, the British Open by a staggering seven strokes. Louis finished the 2010 season in 10th place on the Race to Dubai, posting three further top-10s after his major win.

In January 2011, Oosthuizen claimed his third European Tour title, and his sixth in his home country, winning the Africa Open in a playoff. He successfully defended his title at the Africa Open in 2012 with a two stroke victory, after an impressive second round of 62. 

In 2012 Louis came close to winning his second major title, coming runner-up at the 2012 Masters Tournament. In the final round, he hit an albatross on the second hole of Augusta National Golf Club, taking the outright lead of the tournament until caught on the 16th hole, by Bubba Watson. He was eventually defeated by Watson on the second hole of a sudden-death playoff. Undeterred by this, the following week he won his fifth European Tour title at the Maybank Malaysian Open.