The synthesis of polystyrene-block-poly2-(N-morpholino)ethyl methacrylate (PS-b-PMEMA) as a new highly amphiphilic and multiple stimuli-responsive block copolymer is presented. To achieve high molecular weights far beyond 100 kDa in a highly controlled manner (dispersities < 1.1), a synthetic route via sequential combination of anionic polymerization for the PS block and reversible addition–fragmentation chain transfer (RAFT) polymerization for the PMEMA block is used. The synthesized block copolymers are investigated regarding their microphase separation in bulk, which delivers well-ordered self-assembled bulk structures as evidenced by small-angle x-ray scattering (SAXS) and atomic force microscopy (AFM). In aqueous solution, the block copolymer self-assembles into narrowly size distributed micelles with a PMEMA corona. The stimuli-triggered micelle response towards temperature, pH, and kosmotropic as well as chaotropic salts is shown via various dynamic light scattering (DLS) experiments. Furthermore, a dependency of aggregate size on solvent composition in polymer/tetrahydrofuran/water mixtures is described. The reported findings deliver a feasible pathway to high molecular weight block copolymers with tailored chemical properties and show the potential of PS-b-PMEMA as material for mechanically demanding switchable devices. Display omitted •Polystyrene-block-poly2-(N-morpholino)ethyl methacrylate (PS-b-PMEMA) is highly amphiphilic and multiple stimuli-responsive.•The block copolymers are synthesized via combination of anionic and RAFT polymerization.•High molecular weights far beyond 100 kDa can be obtained.•In bulk, the BCP self-assembles into very distinct microphase-separated structures.•In water, PS-core micelles are formed. The PMEMA corona responds to temperature (in two steps), pH-value and salts.