Weiss was born in Kiel as son of Bernhard Weiss. A perpetual scholar, he studied in the University of Marburg, the University of Berlin, the University of Göttingen, and the University of Breslau. He then taught as a professor at Göttingen in 1890, at Marburg in 1895, and at the University of Heidelberg in 1908. He wrote many influential books and papers, and was instrumental in the development of New Testament Biblical criticism. He was held in the highest regard by his contemporaries, and subsequent scholarship has continued to recognize his wide influence. He died in Heidelberg.
Weiss was famous for making the first comprehensive exegesis of the Gospels from an eschatological perspective. According to Weiss, the "Kingdom of God" was Jesus' understanding of an imminent end to history, and all continuous ethical teachings were additions made by the early church to make Jesus' teaching relevant when the end of the world did not come about immediately. This greatly influenced several generations of Biblical scholars. As a corollary, Weiss believed that the authentic teachings of the historical Jesus would be inapplicable to those who did not hold his first-century apocalyptic worldview.
Weiss also developed form criticism in its application to the New Testament, a theme expanded upon by Rudolf Bultmann and many other scholars. This tool enabled Weiss to conclude that I Corinthians is a collection of excerpts from letters by the Apostle Paul, and not a single letter in its own right.
Weiss is particularly notable for giving the name "Q" to the hypothetical sayings source used by the authors of the Gospel of Matthew and the Gospel of Luke. Many hold that Q stood for "Quelle", the German word for "source", but some recent scholarship indicates that the letter Q was chosen arbitrarily.
Select works 
- Die Predigt Jesu vom Reiche Gottes ("Jesus' Proclamation of the Kingdom of God"), 1892.
- Paulus und Jesus ("Paul and Jesus"), 1909.
- Jesus von Nazareth, Mythus oder Geschichte? ("Jesus of Nazareth, Myth or History?"), 1910.
- Das Urchristentum (completed by R. Knopf as "The History of Primitive Christianity"), 1917.
- Weiss, Johannes. (2007). In Encyclopædia Britannica. Retrieved September 13, 2007, from Encyclopædia Britannica Online: http://www.britannica.com/eb/article-9076463
- F. Crawford Burkitt, Johannes Weiss: In Memoriam, The Harvard Theological Review, Cambridge University Press and Harvard Divinity School, 1915.
- George D. Castor (review author), Johannes Weiss's Commentary on I Corinthians, The American Journal of Theology, The University of Chicago Press, 1911.
- Travis Brouwer, New Testament, Divinity Library. http://www.vanderbilt.edu/AnS/religious_studies/NTBib/quest.html
- John P. Meier, A Marginal Jew Volume II, Doubleday, 1994.