The long blood feeding duration of hard ticks relies on the continuous modulation of saliva composition to manipulate host haemostatic and immune systems. While the exogenous muscarinic acetylcholine receptor (mAChR) agonist, pilocarpine, is a potent inducer of tick salivation, the underlying control mechanisms of endogenous stimulation remain unclear. Here, we characterised two pharmacologically distinct types of mAChRs (A and B) in the genome of the Ixodes ricinus tick. A combination of molecular dynamics and directed mutagenesis revealed the atypical muscarinic profile of the type-B receptor. Immunolabelling followed by in vivo pharmacology and proteomic analyses suggested that the composition of secreted saliva is a result of a complex interplay between different central neurons and specific regions of the salivary gland (SG), mediated by distinct axonal mAChR types. This system likely functions upstream of a neuropeptide signalling cascade, ultimately controlling different salivation subunits in SG. Our study describes a unique model of regulation of tick SG activity in a medically relevant tick species. This knowledge holds broader implications for understanding tick-host interactions.