Conditioned flavor preferences (CFP) are elicited by sucrose relative to saccharin in inbred mice with both the robustness of the preferences and sensitivity to pharmacological receptor antagonists sensitive to genetic variance. Dopamine, opioid and N-methyl-d-aspartate receptor antagonists differentially interfere with the acquisition (learning) and expression (maintenance) of sucrose-CFP in BALB/c and SWR inbred mice. Further, the muscarinic cholinergic receptor antagonist, scopolamine (SCOP) more potently reduces both sucrose and saccharin intake in BALB/c and C57BL/6 relative to SWR inbred mice. The present study examined whether SCOP altered the expression and acquisition of sucrose-CFP in BALB/c, C57BL/6 and SWR mice. In expression experiments, food-restricted mice alternately consumed a flavored (CS+, e.g., cherry, 5 sessions) 16% sucrose solution and a differently-flavored (CS−, e.g., grape, 5 sessions) 0.05% saccharin solution. Two-bottle CS choice tests with the two flavors mixed in 0.2% saccharin solutions occurred following vehicle or SCOP at doses of 1 or 5 mg/kg. SCOP significantly reduced the magnitude of the expression of sucrose-CFP in BALB/c, but not either C57BL/6 or SWR mice. In acquisition experiments, separate groups of BALB/c, C57BL/6 and SWR mice were treated prior to acquisition training sessions with vehicle or 2.5 or 5 mg/kg SCOP doses that was followed by six two-bottle CS choice tests without injections. SCOP dose-dependently reduced (1 mg/kg) and eliminated (2.5 mg/kg) the acquisition of sucrose-CFP in BALB/c mice, and reduced the magnitude of acquisition of sucrose-CFP in SWR mice. In contrast, neither SCOP dose affected the acquisition of sucrose-CFP in C57BL/6 mice. Thus, muscarinic cholinergic receptor signaling is essential for the learning of sucrose-CFP in BALB/c mice, to a lesser degree in SWR mice, but not in C57BL/6 mice. Murine genetic variance differentially modulates muscarinic cholinergic receptor control of sweet intake per se relative to learned conditioned flavor preferences of sweets.