Vibrational strong coupling (VSC) has recently been shown to change the rate and chemoselectivity of ground-state chemical reactions via the formation of light–matter hybrid polaritonic states. However, the observation that vibrational-mode symmetry has a large influence on charge-transfer reactions under VSC suggests that symmetry considerations could be used to control other types of chemical selectivity through VSC. Here, we show that VSC influences the stereoselectivity of the thermal electrocyclic ring opening of a cyclobutene derivative, a reaction which follows the Woodward–Hoffmann rules. The direction of the change in stereoselectivity depends on the vibrational mode that is coupled, as do changes in rate and reaction thermodynamics. These results on pericyclic reactions confirm that symmetry plays a key role in chemistry under VSC. © 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH