Weiss was born at Königsberg. After studying theology at the University of Königsberg (Albertina), Halle and Berlin, he became professor extraordinarius at Königsberg in 1852, and afterwards professor ordinarius at Kiel and Berlin. In 1880 he was made superior consistorial councillor of the Evangelical State Church of Prussia's older Provinces.
An opponent of the Tübingen School, he published a number of important works, which became well known to students in Great Britain and America. He was also the reviser of commentaries on the New Testament in the series of H.A.W. Meyer.
He wrote the commentaries on Matthew (the 9th ed., 1897), Mark and Luke (the 9th ed., 1901), John (the 9th ed., 1902), Romans (the 9th ed., 1899), the Epistles to Timothy and Titus (the 7th ed., 1902), Hebrews (the 6th ed., 1897), and the Epistles of John (the 6th ed., 1900).
His other works include:
- Lehrbuch der biblischen Theologie des Neuen Testaments (1868, 9th ed., 1903; Eng. trans., 1883)
- Des Leben Jesu (1882, 4th ed. 1902; Eng. trans., 1883)
- Lehrbuch der Einleitung in des Neue Testament (1886; 3rd ed., 1897; Eng. trans. 1888)
- Das Neue Testament: Berichtigter Text (3 vols, 1902)
- Die Quellen des Lukasevangeliums (1907)