Rationale High‐precision determination of magnesium (Mg) isotopes can now be routinely achieved by multi‐collector inductively coupled plasma mass spectrometry (MC‐ICP‐MS). The analytical sensitivity and instrumental mass discrimination behavior of this method are, however, sensitive to the types of sample and skimmer cones used in these measurements, so it is important that these parameters should be investigated. Methods Using the sample‐standard‐bracketing method in the wet‐plasma mode, four available combinations of sample and skimmer cones [Jet sample cone + H skimmer cone (Jet + H), standard sample cone + H skimmer cone (Standard + H), standard sample cone + X skimmer cone (Standard + X), and Jet sample cone + X skimmer cone (Jet + X)] were systematically investigated for peak shape, sensitivity, mass discrimination, accuracy, and precision in Mg‐isotopic ratio determination using a Neptune plus MC‐ICP mass spectrometer. Results The results showed that different cone combinations do not affect peak shapes but would significantly change the sensitivities for Mg‐isotopic determinations. Compared with using the Standard + H, the sensitivities of Mg‐isotopic determinations were enhanced by approximately a factor of 1.3, 1.4, and 1.9 by using the Standard + X, the Jet + H, and the Jet + X combinations, with the most stable mass discrimination behaviors obtained by the Jet + H. The instrumental mass fractionation slope for any combination of a modified cone geometry (i.e. Standard + X, Jet + X, and Jet + H) is 0.500, while it is 0.510 for the Standard + H. In addition, the mass discrimination behavior is related to Mg concentrations once the combination is set, indicating the necessity of concentration match during Mg‐isotopic determination. Conclusions The precision and accuracy of the Jet + H combination are better than those of the other combinations, and this is further supported by the validation of the Mg‐isotope data for four international reference materials: Cambridge‐1, NASS‐6, AGV‐2, and BHVO‐2. As the Jet + H combination also provides a high signal, this combination gives the most robust strategy for the highly precise and accurate determination of Mg isotopes.