After completing her schooling, Mohn began an apprenticeship as a dental hygienist. She later applied to become a telephone operator at Bertelsmann and subsequently worked for the company's book club. At the age of 17 she met Reinhard Mohn. In 1963, she married the Editor Joachim Scholz; the couple separated in 1978. In 1982, Reinhard Mohn's first marriage ended in divorce. Liz and Reinhard Mohn married the same year. He adopted their biological children Brigitte Mohn (de), Christoph Mohn (de) and Andreas Mohn (de).

In the following years, Liz Mohn gradually began playing a greater role at the company and foundation: In 1986, she joined the Bertelsmann Stiftung's advisory council. In 1999, she was asked to become a member of the shareholders' meeting of Bertelsmann Verwaltungsgesellschaft, which controls the voting rights at the media group's annual general meeting. In 2000, she also joined the executive committee of the Bertelsmann Stiftung; the foundation indirectly holds a majority of shares in the Bertelsmann group. In 2002, Mohn advanced to the top position at Bertelsmann Verwaltungsgesellschaft, where she also became the family spokesperson; in addition, she joined the supervisory board at Bertelsmann. With that, she took on a leading role overseeing the company.

In 1987, Mohn launched the Neue Stimmen International Singing Competition. She was inspired to do so by Herbert von Karajan, who noted that too little was being done to promote new opera talent. Organized by the Bertelsmann Stiftung, the competition has since become an internationally recognized forum for discovering up-and-coming opera Singers. In addition, Mohn initiated a project in 1999 for promoting music appreciation and education among children, especially in primary schools.

In 1992, she founded the nonprofit German Stroke Foundation (de), which works to prevent and increase awareness of stroke. She was motivated to do so by a medical condition affecting one of her sons which caused symptoms that resembled a stroke. Mohn is President of the foundation and her daughter Brigitte serves as chairwoman of its board of trustees. A key activity in this area is the Roseball, at which Mohn collects donations to be used for fighting the illness.

Liz Mohn has been recognized numerous times for her social engagement. In 1996, she was awarded the European Philanthropy Prize (de), the Grand Cross of the Order of Merit of the Federal Republic of Germany, and the Charity Bambi. In 1999, she was the first woman from Germany to become a full member of the Club of Rome. In 2000, she received the German Medical Association's Badge of Honor. In 2006, the University of Tel Aviv awarded her an honorary doctorate. In 2008, she received UNESCO's Children in Need award. In 2009, she was the first woman to be honored with the Karl Winnacker Prize (de), and she received the Global Economy Prize (de) in 2010. In 2013, Maurice Gourdault-Montagne, France's ambassador to Germany, made her an officer of the French Legion of Honor. In 2014, she received the Euriade Badge of Honor in Gold from Queen Silvia of Sweden. In 2016, Xavier Bettel, prime minister of Luxemburg, awarded her the Commander's Cross of the Order of the Oak Crown.

In 2005, Mohn expanded her efforts to promote music appreciation and education by establishing the Liz Mohn Foundation for Culture and Music. The foundation carries out numerous activities: staging musicals for children and young people, for Example, and awarding scholarships to opera Singers. To achieve its goals, the foundation partners with the Berlin State Opera Unter den Linden and other organizations. It currently has an endowment of €16.2 million and Mohn serves as the chairwoman of its executive board.

Mohn became her husband's successor upon his death in 2009. Among other rights, he had granted her a veto at Bertelsmann Verwaltungsgesellschaft. She was also awarded a majority of the founder's rights at the Bertelsmann Stiftung which allows her, for Example, to propose members for the board of trustees.

In 2016, the Gütersloh city council made Mohn honorary citizen of the city.