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After finishing high school, Busse took private acting lessons in Munich. In 1960, he was discovered at Friedrich Hollaender's student cabaret "Die Knallfrösche" for a cabaret revue in Berlin. Over the next few years, Busse mainly honed his acting and cabaret skills at the Frankfurt cabaret "Die Striche", the "Rationaltheater" in Munich, and Düsseldorf's "Kom(m)ödchen". He also performed in theater productions, including Arthur Miller's "The Death of a Salesman" alongside Horst Tappert, Budjuhn/Rose's "The Twelve Jurors", and Carl Zuckmayer's "The Merry Vineyard". By the late 1960s, he began taking roles in film and television. In 1969, Busse appeared in productions such as "The Young Tigers of Hong Kong" and Wolfgang Becker's "Ellenbogenspiele". He first gained widespread recognition in 1970 playing a murderous drilling engineer in "11:20" alongside Joachim Fuchsberger and Gila von Weitershausen.
In 1972, Busse starred with Charles Regnier in 20 episodes of the ZDF series "Mord Commission", where he also showcased his comedic skills as the clever criminal assistant "Siebenlist". In 1978, he appeared in the television production "Media Clinic". His final serious role was in the 1984 film "The Wannsee Conference". Afterward, he worked as a writer for WDR's "Montagsmagazin" and the NDR children's series "Spencer". He also led his own ARD sketch series titled "Nur für Busse". From 1981 to 1991, Busse was part of the ensemble of the "Munich Laughing and Shooting Society". Alongside Richard Rogler, he co-wrote the script for the six-part entertainment series "Mr. Rogler and Mr. Busse", which premiered on SFB in 1992. In 1994, he appeared with Karsten Speck and others in the ARD sitcom "Three Men in Bed". Starting in February 1996, Busse hosted the popular comedy show "7 Days - 7 Heads" on RTL, which celebrated its 150th episode in April 2001.
The show's team received the "Golden Lion" for "Best Comedy Show" in 1998 and also won a "Bambi" that same year. Busse became a well-known and beloved comedy star. In 2000, he made his directing debut with Heinrich von Kleist's play "The Broken Pitcher" at the Schiller Theater in Wuppertal. That year, Busse was honored with the "German Comedy Prize" for his lifetime achievements. In 2001, he starred in the six-part comedy series "Once a Prince". In August 2002, the political comedy "The Backbenchers" premiered, featuring Busse as part of the cast. He played a leading role in the successful RTL comedy series "Das Amt", which aired its sixth season in 2002 and a seventh in 2003. After many successful years, "7 Days - 7 Heads" aired its final episode on December 30, 2005. A few months later, in April 2006, Busse began hosting the Sat1 comedy talk show "Der Heiße Brei".
In 2007, Busse hosted "Laughing is Fun" on NDR. From late 2007, he toured Germany with Henning Venske in the program "Legend meets Urgestein". Their subsequent joint stage show, titled "Inventur", premiered on September 22, 2009. In 2014, Busse performed solo for the first time with the show "How do I come up with this now?". In 2016, he published the book "Speaking of sandwiches".
