Abstract Scientific, medical, and technological knowledge has transformed our world, but we still poorly understand the nature of scientific methodology. Science textbooks, science dictionaries, and science institutions often state that scientists follow, and should follow, the universal scientific method of testing hypotheses using observation and experimentation. Yet, scientific methodology has not been systematically analyzed using large-scale data and scientific methods themselves as it is viewed as not easily amenable to scientific study. Using data on all major discoveries across science including all Nobel Prize and major non-Nobel Prize discoveries, we can address the question of the extent to which “the scientific method” is actually applied in making science's groundbreaking research and whether we need to expand this central concept of science. This study reveals that 25% of all discoveries since 1900 did not apply the common scientific method (all three features)—with 6% of discoveries using no observation, 23% using no experimentation, and 17% not testing a hypothesis. Empirical evidence thus challenges the common view of the scientific method. Adhering to it as a guiding principle would constrain us in developing many new scientific ideas and breakthroughs. Instead, assessing all major discoveries, we identify here a general, common feature that the method of science can be reduced to: making all major discoveries has required using sophisticated methods and instruments of science. These include statistical methods, particle accelerators, and X-ray methods. Such methods extend our mind and generally make observing, experimenting, and testing hypotheses in science possible, doing so in new ways and ensure their replicability. This provides a new perspective to the scientific method—embedded in our sophisticated methods and instruments—and suggests that we need to reform and extend the way we view the scientific method and discovery process.