Calculus is used in every branch of the physical sciences, actuarial science, computer science, statistics, engineering, economics, business, medicine, demography, and in other fields wherever a problem can be mathematically modeled and an optimal solution is desired. It allows one to go from (non-constant) rates of change to the total change or vice versa, and many times in studying a problem we know one and are trying to find the other.

Physics makes particular use of calculus; all concepts in classical mechanics and electromagnetism are interrelated through calculus. The mass of an object of known density, the moment of inertia of objects, as well as the total energy of an object within a conservative field can be found by the use of calculus. An example of the use of calculus in mechanics is Newton's second law of motion: historically stated it expressly uses the term "rate of change" which refers to the derivative saying The rate of change of momentum of a body is equal to the resultant force acting on the body and is in the same direction. Commonly expressed today as Force = Mass × acceleration, it involves differential calculus because acceleration is the time derivative of velocity or second time derivative of trajectory or spatial position. Starting from knowing how an object is accelerating, we use calculus to derive its path.

Maxwell's theory of electromagnetism and Einstein's theory of general relativity are also expressed in the language of differential calculus. Chemistry also uses calculus in determining reaction rates and radioactive decay. In biology, population dynamics starts with reproduction and death rates to model population changes.

Calculus can be used in conjunction with other mathematical disciplines. For example, it can be used with linear algebra to find the "best fit" linear approximation for a set of points in a domain. Or it can be used in probability theory to determine the probability of a continuous random variable from an assumed density function. In analytic geometry, the study of graphs of functions, calculus is used to find high points and low points (maxima and minima), slope, concavity and inflection points.

Green's Theorem, which gives the relationship between a line integral around a simple closed curve C and a double integral over the plane region D bounded by C, is applied in an instrument known as a planimeter which is used to calculate the area of a flat surface on a drawing. For example, it can be used to calculate the amount of area taken up by an irregularly shaped flower bed or swimming pool when designing the layout of a piece of property.

In the realm of medicine, calculus can be used to find the optimal branching angle of a blood vessel so as to maximize flow. From the decay laws for a particular drug's elimination from the body, it's used to derive dosing laws. In nuclear medicine, it's used to build models of radiation transport in targeted tumor therapies.

In economics, calculus allows for the determination of maximal profit by providing a way to easily calculate both marginal cost and marginal revenue.

Calculus is also used to find approximate solutions to equations; in practice it's the standard way to solve differential equations and do root finding in most applications. Examples are methods such as Newton's method, fixed point iteration, and linear approximation. For instance, spacecraft use a variation of the Euler method to approximate curved courses within zero gravity environments.