The Paraguayan was joined in the play-off by Henrik Stenson, Rafael Cabrera-Bello and Gregory Havret after finishing level on 19-under par in the final round.
It would take until the fifth extra hole for Zanotti to secure victory, with Havret and Cabrera-Bello forced out of the running on the second and fourth extra holes respectively.
Zanotti is now the first golfer from his country to win on the European Tour, going one better on his second-place finishes at the 2009 Open de Espana, 2010 KLM Open and 2012 Irish Open.
Cabrera-Bello had been the favourite to triumph in the play-off tussle since he had carded an eagle and a birdie on the 17th and 18th holes. Those were impressive moments in his round, but there Zanotti had shown greater consistency given that he was alone among the four leaders in not having bogeyed a hole in the fourth navigation of the Cologne course.
"I have really been playing very well in the last few weeks so I knew that if I had a good round I would have a good chance," said the 31-year-old. "I have been working a lot and trying to bring up my confidence to get to this moment."
Stenson, ranked second in the world and second in Cologne, appeared to be in control as he teed off at the first extra hole, with his approach bringing the prospect of a birdie. However, his miss kept all four players in the hunt.
The Swede seemed to recover with a birdie on the next hole as France's Havret was forced to surrender his ambition. Stenson - who won the BMW International via a play-off in 2006 - then missed an eagle putt as the remaining players scored birdies to take the play-off to a fourth hole.
As the rain fell, so did Cabrera-Bello. Zanotti also suffered a wobble when he missed a birdie opportunity, with Stenson having pitched to within a few feet of the pin. As they returned to the 18th, Stenson followed Cabrera-Bello into the water and Zanotti fell short of the green but, crucially, stayed on dry land.
Stenson then found himself marooned as he failed to make a shot from a bunker and the Swede conceded his hopes of winning the tournament.
Zanotti was able to celebrate and also to reflect on an entertaining day. Simon Dyson of England might have joined him in the play-off had he not bogeyed the 12th to finish on 18 under overall. Overnight leader Pablo Larrazabal slipped a shot further behind.