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Physics educators today face two major challenges: supporting the acquisition of a solid base of conceptual knowledge and reducing the persisting gender gap. In the present quasi-experimental study, we investigated the potential of physics instruction that is enriched with evidence-based cognitively activating methods, such as inventing with contrasting cases or metacognitive questions, to overcome both of these challenges. Four physics teachers in charge of two parallel classes each applied our cognitively activating instruction in one of their classes (CogAct classes). The other classes received regular physics lessons (regular classes) on the same content. The sample consisted of 172 individuals from the advanced track of Swiss secondary school. Controlling for several individual student variables, CogAct classes (N = 87) outperformed regular classes (N = 85) in conceptual understanding at posttest (p < .01, β = 0.19, 95% CI [0.07, 0.32]) and three months later (p < .05, β = 0.13, 95% CI [0.00, 0.26]). The CogAct classes’ advantage in conceptual understanding was not at the expense of their quantitative problem-solving performance, which even exceeded the quantitative problem-solving performance of the regular classes at posttest (p < .05, β = 0.14, 95% CI [0.00, 0.28]). In addition, female students with above-average intelligence (PR >75) particularly benefited from CogAct instruction, as indicated by descriptive statistics and the interaction between intelligence and condition in the group of the female students for posttest conceptual understanding (p < .05, β = 0.88, 95% CI [0.06, 1.69]). We conclude that teachers can successfully be supported in implementing cognitively activating methods that improve their students’ conceptual understanding and reduce the gender gap in physics.