Otto studied chemistry at the University of Groningen and in 1994, he received his Master's degree, focusing on physical organic chemistry and biochemistry, with the distinction cum laude. In 1998, he obtained his PhD, again with the distinction cum laude, from his supervisor Prof. Jan B.F.N. Engberts for his thesis entitled Catalysis of Diels-Alder reactions in water.
After his subsequent research in both the United States (in 1998, with Prof. Steven L. Regen) at Lehigh University and in the United Kingdom (first with Prof. Jeremy K.M. Sanders and then, from 2001 onwards, as a Royal Society University Research Fellow, both at the University of Cambridge), he was appointed assistant professor at the University of Groningen in 2009. In 2011, he was promoted to associate professor and in 2016, to full professor. From 2014 to 2019, he coordinated the master's degree programme in chemistry.
Alongside his work at the university, Otto is also one of the six principal investigators of the Dutch national gravity programme for functional molecular systems (FMS; €26 million, over 10 years, 2013–2023). The ambition of this programme is to gain control over molecular self-assembly. With this technology, nanomotors could be made, for example, or biomaterials to repair damaged bodily tissues.
Otto was the lead applicant and chair of the European Cooperation in Science & Technology (COST) Action CM1304 (Emergence and Evolution of Complex Chemical Systems), which united more than 95 European research groups. He is the chair of the Gordon Research Conference on Systems Chemistry 2020  and is editor-in-chief of the Journal of Systems Chemistry.
Otto is a member of the Royal Dutch Chemical Society (KNCV),  fellow of the Royal Society of Chemistry and member of the American Chemical Society. He is member of the steering committee of the Origins Center. The Origins Center is a Dutch research platform for scientists who are involved in the key questions of the Dutch Research Agenda on the origin, evolution and future of life on Earth and in the universe. Otto is active on several fronts in both the Netherlands and abroad. Otto was elected a member of the Royal Netherlands Academy of Arts and Sciences in 2020.