We present a theoretical study of the ultrafast dynamics in noble metal clusters interacting with molecular oxygen which is of fundamental importance for the understanding and design of cluster-based heterogenous nanocatalysts. We demonstrate that intrinsic dynamical properties can significantly promote the reactivity of small noble metal clusters towards O 2 . This concept is illustrated by performing collision simulations between Ag6- and Au6- clusters and O 2 in the framework of the ab initio molecular dynamics (MD) using density functional theory (DFT). We show that different nature and efficiency of the internal vibrational energy redistribution (IVR) during the collisions with O 2 are responsible for considerably different sticking probabilities of O 2 to silver and gold clusters, respectively. In the case of Au6-+O2, resonant IVR between the cluster and the O 2 subunit activates the O–O bond and promotes the subsequent oxidation reaction. In contrast, in the case of Ag6-+O2 fast dissipative IVR on the time scale of ∼1ps leads to a higher sticking probability for O 2 but the O–O bond is very rapidly deactivated and cannot participate in further oxidation processes. These findings allow us to introduce the nature of IVR as a criterion for promoting the reactivity of noble metal clusters. Such different behaviour of silver and gold clusters colliding with O 2 originates from difference in relativistic effects which are considerably more pronounced in the case of gold clusters causing more directional rigid bonding in contrast to silver clusters with more s-metallic floppy character. Moreover, we demonstrate that breaking of O–O bond can be induced in Au6O2- by a selective excitation of the O–O bond with an ultrashort pulse in the infrared spectral range. This opens the perspective to control the action of nanocatalysts by employing shaped laser pulses and thus bridges the fields of femtochemistry and cluster nanocatalysis.