Bertarelli was CEO and Deputy Chairman of Serono, a Swiss biotechnology company he inherited from his father Fabio. Under his leadership, Serono shifted its focus from pharmaceuticals to biotechnology and revenues increased from $809 million in 1996 to $2.8 billion in 2006. The company gained fame from its discovery of a natural hormone used in the treatment of female infertility. Serono was sold to Merck KGaA of Germany in September 2006 for US$13.3 billion, forming a new company Merck-Serono.
In 2000, Bertarelli founded the yachting syndicate Team Alinghi, which in 2003, representing the Société Nautique de Genève, won the Louis Vuitton Cup before beating Team New Zealand in Auckland to win the America's Cup. It was the first time a team had ever won the coveted sailing trophy on its first attempt and the victory brought the Cup back to Europe for the first time since 1851. Ernesto himself served as navigator in 2003 and as an afterguard runner and grinder on the boat in 2007, when Alinghi defended the America's Cup in Valencia, Spain.
The event organised by the Swiss with a completely new format proved to be an outstanding success. On July 3, 2007, Team Alinghi beat Team New Zealand over the line by 1 second to retain the America's Cup, winning the series 5-2. Bertarelli said the evening during the Swiss news on TV in reference to his former skipper that "Russell Coutts memory is now over" . Bertarelli and Coutts had parted away in bitter terms during the Cup.
In recognition of his success, Bertarelli was given the Légion d’Honneur by President Jacques Chirac of France, and the Cavaliere di Gran Croce by Carlo Azeglio Ciampi, President of the Italian Republic.
His current business and finance interests include an investment management group and the Ares Life Sciences private equity vehicle which builds on his extensive industry knowledge. Since 2002, he has served as a board director of UBS AG. He is a member of the Strategic Advisory Board at Ecole Polytechnique Fédérale de Lausanne (EPFL) and of the Harvard Medical School Board of Fellows, and in 2008 he was inducted into the Babson College Academy of Distinguished Entrepreneurs.
Bertarelli’s philanthropic activities are run through the Bertarelli Foundation, created together with his sister Dona and their mother. It is dedicated to numerous non-lucrative initiatives in the fields of charity, health, sciences, sport and culture.
Bertarelli is ranked 76 in an annual ranking of the world's wealthiest people compiled and published by Forbes magazine in March 2007. His personal wealth was estimated by Forbes' List of billionaires (2007) at US$8.8 billion.