Loitzl, 28, bagged his first major win after jumps of 134.5m and 136.5m gave him 276.3 points, enough to see off Switzerland's double 2002 Olympic champion and opening leg winner Simon Ammann, who is hoping to land his countrymen their first overall success in the event.
Ammann could only manage 274.6 points after he jumped 140m and 134.5m while Finn Harri Olli scored 258.6 points with 133m and 131.5m to complete the podium.
The third leg of the event is in Innsbruck on Sunday prior to Tuesday's final leg at Bischofshofen.
Titleholder Janne Ahonen of Finland, who managed a record five overall Four Hills wins, retired last spring.
Ammann thought his opening gambit would suffice but the World Cup leader's second jump meant he just missed out as Loitzl's own second jump received a maximum score of 20 from four of the five judges.
"It was a great jump - doubtless the best I have ever pulled off," said Loitzl. "I knew that pulling out something like that was the only way to worry Ammann."
Loitzl had beforehand come close on numerous occasions with six second places and three third places in his career but this time made the breakthrough.
Loitzl now leads Ammann by 561.5 points to 561.0 in the competition but the Swiss leads the World Cup overall standings after nine of 28 events with 765 points to Austrian Gregor Schlierenzauer's 610 and 539 for Loitzl.