Around schooling age, his father, Johann, encouraged him to study Business, there being poor rewards awaiting a Mathematician. However, Daniel refused, because he wanted to study mathematics. He later gave in to his father's wish and studied Business. His father then asked him to study in Medicine, and Daniel agreed under the condition that his father would teach him mathematics privately, which they continued for some time. Daniel studied Medicine at Basel, Heidelberg, and Strasbourg, and earned a PhD in anatomy and botany in 1721.

His earliest mathematical work was the Exercitationes (Mathematical Exercises), published in 1724 with the help of Goldbach. Two years later he pointed out for the first time the frequent desirability of resolving a compound motion into motions of translation and motion of rotation. His chief work is Hydrodynamica, published in 1738; it resembles Joseph Louis Lagrange's Mécanique Analytique in being arranged so that all the results are consequences of a single principle, namely, conservation of Energy. This was followed by a memoir on the theory of the tides, to which, conjointly with the memoirs by Euler and Colin Maclaurin, a prize was awarded by the French Academy: these three memoirs contain all that was done on this subject between the publication of Isaac Newton's Philosophiae Naturalis Principia Mathematica and the investigations of Pierre-Simon Laplace. Bernoulli also wrote a large number of papers on various mechanical questions, especially on problems connected with vibrating strings, and the solutions given by Brook Taylor and by Jean le Rond d'Alembert.

In Hydrodynamica (1738) he laid the basis for the kinetic theory of gases, and applied the idea to explain Boyle's law.

In May, 1750 he was elected a Fellow of the Royal Society.

According to Léon Brillouin, the principle of superposition was first stated by Daniel Bernoulli in 1753: "The general motion of a vibrating system is given by a superposition of its proper vibrations."

One of the earliest attempts to analyze a statistical Problem involving censored data was Bernoulli's 1766 analysis of smallpox morbidity and mortality data to demonstrate the efficacy of vaccination.

Soon Physicians all over Europe were measuring patients' blood pressure by sticking point-ended glass tubes directly into their arteries. It was not until about 170 years later, in 1896 that an Italian Doctor discovered a less painful method which is still in use today. However, Bernoulli's method of measuring pressure is still used today in modern aircraft to measure the speed of the air passing the plane; that is its air speed.