He studied mathematics at the Catholic University of Leuven under his uncle Louis-Philippe Gilbert, after he had earned his bachelor's degree in engineering.

In August 1914, de la Vallée Poussin escaped from Leuven at the time of its destruction by the invading German Army of World War I, and he was invited to teach at Harvard University in the United States.

After the war was over, de la Vallée Poussin returned to Belgium, The International Union of Mathematicians was created, and he was invited to become its President.

Between 1918 and 1925, de la Vallée Poussin traveled extensively, lecturing in Geneva, Strasbourg, and Madrid.

[1] De la Vallée Poussin was given the titles of Doctor Honoris Causa of the Universities of Paris, Toronto, Strasbourg, and Oslo, an Associate of the Institute of France, and a Member of the Pontifical Academy of Sciences,[2] Nazionale dei Lincei, Madrid, Naples, Boston.

In 1961, de la Vallée Poussin fractured his shoulder, and this accident and its complications led to his death in Watermael-Boitsfort, near Brussels, Belgium, a few months later.

[3] A student of his, Georges Lemaître, was the first to propose the Big Bang theory of the formation of the Universe.

Although his first mathematical interests were in analysis, he became suddenly famous as he proved the prime number theorem independently of his coeval Jacques Hadamard in 1896.

It was in 1912, "the only textbook on analysis containing both Lebesgue integral and its application to Fourier series, and a general theory of approximation of functions by polynomials".

Starting from the eighth edition, Fernand Simonart took over the revision and the publication of the Cours d’analyse.