The points of departure for this paper are two of the most important facets of Xenakis’ work, namely his profound interest for the notion of randomness, which acts as both an inspirational force and an operational tool, and his attachment to mathematics, which is for him a kind of “guardrail”, as Mâkhi Xenakis had once said. Randomness is often seen as indeterminacy, unpredictability, uncontrollability; as regularity or, on the contrary, as irregularity or singularity; as the impossibility of repetition; as the “mesure of our ignorance” – if we borrow the words from the mathematician Henri Poincaré –, or as the incapacity to recognize a subject in some circumstances… “Randomness is the subject of the verb ‘to choose’ when this subject is unknown, or impossible to know, or even does not exist”, as the biologist Albert Jacquard puts it in this elegant and intriguing formula. The paper explores from a philosophical and a mathematical point of view the notions of randomness, indeterminacy and unpredictability, and questions their role in some creative processes in music and architecture, from the stochastic music by Iannis Xenakis using classical mathematics, to his algorithmic investigations and to some aspects of the “parametricism” and multi-agent systems in contemporary architecture. We will try to point out the differences between the three notions: randomness, indeterminacy and unpredictability, which are often used almost indistinguishably in common language, and question their capacity to motivate innovating design processes. Xenakis himself, in a late article entitled “Determinacy and indeterminacy” (1996), clarifies the meaning of these notions in contemporary science and explains their transposition and application in musical composition, without omitting to mention the semantic distance between the scientific definition and his artistic interpretation. We then will try to show the three levels of application of randomness by Xenakis in his musical compositions: first, as a particular type of indeterminism; second, the implementation of mathematical formulas coming from probabilistic theories; third, the use of random values. More generally, we will try to qualify the evolution in the use of mathematics in Xenakis’ work both in music and architecture. Questioning the of mathematics by Xenakis, we will underline the profoundly structural role that he attributes to mathematical formalisation as well as the fact that he ultimately transforms a descriptive tool – the equations and functions to which are reduced some natural phenomena – to a generative one capable of producing aesthetical value and meaning. We will finally move from probabilistic theories and mathematical formalisation to cellular automata and computational procedures, and from top-down approaches towards bottom-up ones, trying to unveil the different tendencies that exist explicitly or latently in Xenakis’ heritage and that can be found in contemporary architectural or artistic actions, or even inspire new ways of creation.