Spontaneous focusing on quantitative relations (SFOR) is related to the development of rational number knowledge and predicts future mathematical knowledge. However, scarce evidence exists on whether and how SFOR tendency can be supported with classroom instruction. In this quasi-experimental study, 306 5th grade students participated in one of two four-lesson interventions. We investigated the relative effectiveness of both interventions on students’ SFOR tendency and their knowledge of multiplicative relations and fractions. Students in the Spot the Relations intervention (n = 142) completed activities that supported their ability to recognize and describe multiplicative relations in their everyday surroundings. Students in the Fraction Estimation Game intervention (n = 164) trained with digital game-based number line estimation tasks that supported their fraction knowledge. The results revealed that students in the first group showed larger gains in their multiplicative relations knowledge and SFOR tendency, whereas those in the second group showed larger gains in their fraction knowledge from pre- to posttest. Although SFOR tendency was supported by both interventions over time, the effect was larger for Spot the Relations, which used instructional practices that supported students’ multiplicative knowledge and mathematical language and made multiplicative relations relevant and observable parts of the world.