He studied at both the universities of Zurich and Berlin, receiving his doctorate in theology from Zurich in 1913. The title of his doctoral dissertation was: The Symbolic Element in Religious Knowledge. Brunner served as pastor from 1916 to 1917 in the mountain village of Obstalden in the Canton of Glarus. He spent a year in New York, USA at Union Theological Seminary studying (1919–1920).
In 1921 Brunner wrote what he considered a second dissertation: Experience, Knowledge and Faith. Soon, another book followed: Mysticism and the Word. This work was a devastating critique of the liberal theology of Friedrich Schleiermacher. Brunner was rewarded for his literary efforts with the appointment as the professor of Systematic and Practical Theology at the University of Zurich from 1924–1955. In the next few years his reputation continued to increase particularly with the publication of two more books, the first The Philosophy of Religion from the Standpoint of Protestant Theology, and second The Mediator.
In 1932, following a few years of receiving invitations to visit and lecture across Europe and the United States, and accepting them, Brunner wrote God and Man and The Divine Imperative. Brunner continued his theological output with Man in Revolt and Truth as Encounter in 1937. In 1938–1939 he again visited the US when he agreed to a visiting professorship at Princeton Theological Seminary.
He returned to Europe prior to World War II along with a young Scottish theologian (a student of Karl Barth's in Basel) T. F. Torrance who was teaching at Auburn Theological Seminary. Torrance would later distinguish himself at the University of Edinburgh. Following the war, Brunner was invited to give the distinguished Gifford Lectures at the University of St. Andrews, (1946–1947) in Scotland, the title of his lectures being Christianity and Civilization. His teaching career concluded in 1953–1955 at what was then the new International Christian University in Tokyo, Japan, but not before the publication of his three volume Dogmatics. Volume One was titled: The Christian Doctrine of God. Volume Two was titled: The Christian Doctrine of Creation and Redemption, and the final volume was titled: The Christian Doctrine of the Church, Faith, and Consummation. On the return journey from Japan to Europe, Brunner suffered a cerebral hemorrhage and was physically impaired weakening his ability to work productively. Though there were times when he felt better during the next nine years, he suffered further strokes off and on, finally succumbing to death in 1966.
Brunner undoubtedly holds a place of prominence in Protestant theology in the 20th century and was one of the four or five system builders.
Brunner rejected liberal theology's (particularly European) portrait of Jesus Christ as merely a highly-respected human being. Instead, Brunner insisted that Jesus was God incarnate and central to salvation. Some observers claim that Brunner also attempted to find a middle position within the ongoing Arminian and Calvinist debate, stating that Christ stood between God's sovereign approach to humankind and free human acceptance of God's gift of salvation. However, as Brunner was a German-speaking European to whose heritage Arminianism did not belong, it may be more accurate to describe his viewpoint as a melding together of Lutheran and Reformed perspectives upon soteriology. In any case, Brunner and his compatriots in the neoorthodox movement all rejected, in toto with other humanist conceptions of Christianity prominent in the late 19th century, Pelagian concepts of human cooperation with God in the act of salvation. They embraced Augustine's views instead, especially as refracted through Martin Luther.
Although Brunner re-emphasized the centrality of Christ, evangelical and fundamentalist theologians have usually rejected Brunner's other teachings, including his dismissal of certain "miraculous" elements within the Scriptures and his questioning of the usefulness of the doctrine of the inspiration of the Bible. This is in accord with the treatment they have afforded others in the movement such as Barth and Paul Tillich; most conservatives have viewed neoorthodox theology as simply a more moderate form of liberalism, rejecting its claims as a legitimate expression of the Protestant tradition.