Mercator, originally named Kremer, was born at Rupelmonde, now in Belgium. At the University of Louvain (1530–32) he was a pupil of Gemma Frisius. After learning the basic skills of an instrument maker and engraver, he founded his own studio in Louvain in 1534. Despite accusations of heresy and imprisonment in 1544, he remained in Louvain until 1552, when he moved to Duisburg and opened a cartographic workshop.

Mercator first made his international reputation as a cartographer in 1554 with his map of Europe in which he reduced the size of the Mediterranean from the 62° of Ptolemy to a more realistic, but still excessive, 52°. He produced his world map in 1569 and his edition of Ptolemy in 1578, while his Atlas, begun in 1569, was only published by his son after his death. It was intended to be a whole series of publications describing both the creation of the world and its subsequent history. Mercator was the first to use the term ‘atlas’ for such works, the book having as its frontispiece an illustration of Atlas supporting the world.

The value of Mercator's work lies not just in his skills as an engraver, but also in the introduction of his famous projection in his 1569 map of the world. Navigators wished to be able to sail on what was called a rhumb-line course, or a loxodrome, i.e., to sail between two points on a constant bearing, charting their course with a straight line. On the surface of a globe such lines are curves; to project them onto a plane chart Mercator made the meridians (the lines of longitude) parallel instead of converging at the Poles. This made it straightforward for a navigator to plot his course but it also produced the familiar distortion of the Mercator projection – exaggeration of east–west distances and areas in the high latitudes.

The big difference, apart from projection, between Mercator's and classical maps was in the representation of the Americas. He was not the first to use the name America on a map, that distinction belonging to Martin Waldseemüller in 1507, but he was the first to divide the continent into two named parts – Americae pars septentrionalis (northern part of America) and Americae pars meridionalis (southern part of America).