Animals depend on fast and reliable detection of novel stimuli in their environment. Neurons in multiple sensory areas respond more strongly to novel in comparison to familiar stimuli. Yet, it remains unclear which circuit, cellular, and synaptic mechanisms underlie those responses. Here, we show that spike-timing-dependent plasticity of inhibitory-to-excitatory synapses generates novelty responses in a recurrent spiking network model. Inhibitory plasticity increases the inhibition onto excitatory neurons tuned to familiar stimuli, while inhibition for novel stimuli remains low, leading to a network novelty response. The generation of novelty responses does not depend on the periodicity but rather on the distribution of presented stimuli. By including tuning of inhibitory neurons, the network further captures stimulus-specific adaptation. Finally, we suggest that disinhibition can control the amplification of novelty responses. Therefore, inhibitory plasticity provides a flexible, biologically plausible mechanism to detect the novelty of bottom-up stimuli, enabling us to make experimentally testable predictions.