Wendelen was born in Herk-de-Stad in the Prince-Bishopric of Liège (now Belgian Limburg) on 6 June 1580. His parents were Nicolaas, an alderman of Herk, and Elisabeth Corneli. By his own account, he first observed a lunar eclipse as a schoolboy, on 30 December 1591: it ended at quarter to six in the morning, giving him just time to get to school for his first class at six o'clock.
After studying at the Latin school in Herk he matriculated at the University of Leuven, where he studied the liberal arts under Justus Lipsius. He was a close personal friend of Lipsius's successor, Erycius Puteanus. Intending to study with Tycho Brahe Wendelinus set off for Prague, but was stopped en route by an illness that necessitated his return to the Low Countries. He then spent several years in Provence. In 1599 he established the latitude of Marseille. In 1600 he travelled to Rome for the Holy Year, and then became a mathematics teacher in Digne. In 1604 he was a private tutor in the household of André d'Arnauld in Forcalquier.
In 1612 he obtained the degree of Doctor of both laws from the University of Orange. In the same year he returned to Herk for family reasons and became head of the Latin school in the town. He also began to study for the priesthood, and he was ordained in Mechelen by Mathias Hovius on 4 April 1620. He was appointed parish priest of Geetbets, which he remained until 1632. His time as parish priest was marked by disputes concerning tithes with the abbot of Vlierbeek and the provost of the Church of St. Denis (Liège), and by the keeping of an unusually meticulous parish register. It was while at Geetbets that he published Loxias seu de obliquitate solis (Antwerp, Hieronymus Verdussen, 1626), a critical overview of ancient and medieval astronomy.
Around 1630 he measured the distance between the Earth and the Sun using the method of Aristarchus of Samos. The value he calculated was 60% of the true value (243 times the distance to the Moon; the true value is about 384 times; Aristarchus calculated about 20 times).
From 1633 to 1650, Wendelinus was parish priest of his home town, Herk-de-Stad. In 1633 he was also assigned a prebend in the collegaite church of Condé, to provide an income that would support his scientific work. This led to contacts with Douai University and to researches in early Christian chronology. One of his main works, Eclipses lunares ab anno 1573 ad 1643 observatae (Lunar eclipses observed from the year 1573 to 1643), was published during this period.