Weierstrass was born in Ostenfelde, part of Ennigerloh, Province of Westphalia. He was the son of Wilhelm Weierstrass, a government official, and Theodora Vonderforst. His interest in mathematics began while he was a Gymnasium student. He was sent to the University of Bonn upon graduation to prepare for a government position. Because his studies were to be in the fields of law, economics, and finance, he was immediately in conflict with his hopes to study mathematics. He resolved the conflict by paying little heed to his planned course of study, but continued private study in mathematics. The outcome was to leave the university without a degree. After that he studied mathematics at the Academy in Münster and his father was able to obtain a place for him in a teacher training school in Münster. Later he was certified as a teacher in that city. During this period of study, Weierstrass attended the lectures of Christoph Gudermann and became interested in elliptic functions.

After 1850 Weierstrass suffered from a long period of illness, but was able to publish papers that brought him fame and distinction. He took a chair at the Technical University of Berlin, then known as the Gewerbeinstitut. He was immobile for the last three years of his life, and died in Berlin from pneumonia.

Weierstrass was interested in the soundness of calculus. At the time, there were somewhat ambiguous definitions regarding the foundations of calculus, and hence important theorems could not be proven with sufficient rigour. While Bolzano had developed a reasonably rigorous definition of a limit as early as 1817 (and possibly even earlier) his work remained unknown to most of the mathematical community until years later, and many had only vague definitions of limits and continuity of functions.

Cauchy gave a form of the (ε, δ)-definition of limit, in the context of formally defining the derivative, in the 1820s, but did not correctly distinguish between continuity at a point versus uniform continuity on an interval, due to insufficient rigor. Notably, in his 1821Cours d'analyse, Cauchy gave a famously incorrect proof that the (pointwise) limit of (pointwise) continuous functions was itself (pointwise) continuous. The correct statement is rather that the uniform limit of uniformly continuous functions is uniformly continuous. This required the concept of uniform convergence, which was first observed by Weierstrass's advisor, Christoph Gudermann, in an 1838 paper, where Gudermann noted the phenomenon but did not define it or elaborate on it. Weierstrass saw the importance of the concept, and both formalized it and applied it widely throughout the foundations of calculus.

The (ε, δ)-definition of limit, as formulated by Weierstrass, is as follows:

 is continuous at  if for every  such that

Using this definition and the concept of uniform convergence, Weierstrass was able to write proofs of several then-unproven theorems such as the intermediate value theorem (for which Bolzano had given an insufficiently rigorous proof), the Bolzano-Weierstrass theorem, and Heine-Borel theorem.

Weierstrass also made significant advancements in the field of calculus of variations. Using the apparatus of analysis that he helped to develop, Weierstrass was able to give a complete reformulation of the theory which gave way for the modern study of calculus of variations. Among several significant results, Weierstrass established a necessary condition for the existence of strong extrema of variational problems. He also helped devise the Weierstrass–Erdmann condition which gives sufficient conditions for an extremal to have a corner.