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In Neu-Kölln, he attended the Catholic private school St. Marien and served as an altar boy during his teenage years. After finishing school, Barth completed an apprenticeship as a telecommunications system electronics technician at Siemens before enrolling in acting school. He honed his comedic skills in comedy workshops and gained initial experience through brief appearances on TV shows like Nonsense Comedy Club. In 2001, Barth launched his own live comedy show, focusing from the outset on the dynamics between men and women with his program "Men are pigs, but so are women!" That same year, he presented the show "Men are primitive but happy!" and received the German Comedy Prize for Best Live Comedy. He also appeared in the RTL program "Mario sucht das Paradies," portraying roles such as a cowboy, fireman, and pilot.
Though many reviews labeled his work as light entertainment, in 2003 Barth secured his own show on the private channel ProSieben. The first season of "I have no idea?" aired, followed by a second season in 2005, totaling ten episodes. He also featured in the Sat1 comedy program Schillerstrasse, playing a heating engineer and other characters, as well as in RTL's "Typisch Frau - Typisch Mann." His live DVD of "Men are pigs, but so are women!" was released in 2005, recorded at Berlin's Olympic Stadium, and reached number 3 on the German album charts. The Berlin comedian earned ten times platinum for selling over two million copies. In 2007, audiences saw him on the RTL show "Mario Barth presents."
In 2008, his record-breaking show at Berlin's Olympic Stadium was released as a CD titled "Men are primitive, but happy!" which also featured the single "Mensch Berlin." His first film, "Männersache," released in 2009, similarly explored male-female relationships. That year, he also launched his audio CD "Männersache" and began hosting the RTL program "Welcome to Mario Barth." In 2010, a CD compiling three live programs—"Men are pigs, but so are women!", "Men are primitive, but happy!", and "Men are embarrassing, women sometimes too!"—was released. In 2011, Barth toured four major stadiums with the last program, performing at Commerzbank Arena in Frankfurt am Main, Veltins Arena in Gelsenkirchen, Red Bull Arena in Leipzig, and the Olympic Stadium in Berlin, attracting over 200,000 attendees.
In 2012, Mario Barth embarked on a tour with his fourth live show, "Men are to blame, say women.
