Born in the Duchy of Prussia's capital Königsberg, part of Brandenburg - Prussia, Goldbach was the son of a pastor. He studied at the Royal Albertus University. After finishing his studies he went on long educational voyages from 1710 to 1724 through Europe, visiting other German states, England, Holland, Italy, and France, meeting with many famous mathematicians, such as Gottfried Leibniz, Leonhard Euler, and Nicholas I Bernoulli. Back in Königsberg he got acquainted with Georg Bernhard Bilfinger and Jakob Hermann.

He went on to work at the newly opened St Petersburg Academy of Sciences in 1725. Later on, he was a tutor to the later Tsar Peter II in 1728. In 1742 he entered the Russian Ministry of Foreign Affairs.

Goldbach is most noted for his correspondence with Leibniz, Euler, and Bernoulli, especially in his 1742 letter to Euler stating his Goldbach's Conjecture. He also studied and proved some theorems on perfect powers, such as the Goldbach - Euler theorem, and made several notable contributions to analysis.