After completing his university studies, Kossel returned to the University of Strassburg as research assistant to Felix Hoppe-Seyler. At the time, Hoppe-Seyler was intensely interested in research concerning an acidic substance that had first been chemically isolated from pus cells by one of his former students, Friedrich Miescher, in 1869. Unlike protein, the substance contained considerable amounts of phosphorus, but with its high acidity, it was unlike any cellular substance that had yet been observed.

In 1872, Kossel attended the University of Strassburg to study Medicine. He studied under Felix Hoppe-Seyler, who was head of the department of biochemistry, the only such institution in Germany at the time. He attended lectures by Anton de Bary, Waldeyer, August Kundt, and Baeyer. He completed his studies at University of Rostock, and passed his German medical license exam in 1877.

Kossel contributed to early issues of the Zeitschrift für Physiologische Chemie (Journal of Physiological Chemistry). This publication was founded by his professor and mentor, Felix Hoppe-Seyler, in 1877, the same year that Kossel started work as his research assistant. After Hoppe-Seyler's death in 1895, Kossel took over editorship of the Zeitschrift and continued in that role until his own death in 1927.

In 1883, Kossel left Strassburg to become Director of the Chemistry Division of the Physiological Institute at the University of Berlin. In this post, he succeeded Eugen Baumann and worked under the supervision of Emil du Bois-Reymond.

Kossel continued his previous work on the nucleic acids. During the period 1885 to 1901, he was able to isolate and name its five constituent organic compounds: adenine, cytosine, guanine, thymine, and uracil. These compounds are now known collectively as nucleobases, and they provide the molecular structure necessary in the formation of stable DNA and RNA molecules.

In 1886, Kossel married Luise Holtzman, daughter of Adolf Holtzmann. Holtzmann was Professor at the University of Heidelberg, lecturing in German literature as well as Sanskrit. He was also a noted philologist of his day. The couple had three children, two of whom survived to maturity: Walther, born in 1888, and daughter Gertrude, born in 1889.

Son Walther Kossel (1888–1956) became a prominent Physicist and was professor of theoretical physics and Director of the Physics Institute at the University of Tübingen. He is known for his theory of the chemical bond (ionic bond/octet rule), the Sommerfeld–Kossel displacement law, and other achievements.

In 1895, Kossel was professor of physiology as well as Director of the Physiological Institute at the University of Marburg. Around this time, he began investigations into the chemical composition of proteins, the alterations in proteins during transformation into peptone, the peptide components of cells, and other investigations.

In 1896, Kossel discovered histidine, then worked out the classical method for the quantitative separation of the "hexone bases" (the alpha-amino acids arginine, histidine, and lysine). He was also the first to isolate Theophylline, a therapeutic drug found naturally in tea and cocoa beans.

In 1901, Kossel was named to a similar post at Heidelberg University, and became Director of the Heidelberg Institute for Protein Investigation. His research predicted the discovery of the polypeptide nature of the protein molecule.

Another of Kossel's students was American biochemist Edwin B. Hart, who would later return to the United States to participate in the "Single-grain experiment" (1907–1911) and be part of research teams that would determine the nutritive causes of anemia and goiter. Another was Otto Folin, an American Chemist who discovered Phosphocreatine.

Kossel was awarded the Nobel Prize in Physiology or Medicine in 1910 for his research in cell biology, the chemical composition of the cell nucleus, and for his work in isolating and describing nucleic acids. The award was presented on 10 December 1910.

In the autumn of 1911, Kossel was invited to the United States to deliver the Herter Lecture at Johns Hopkins. Traveling with his wife Luise and daughter Gertrude, he took the opportunity to travel and to visit acquaintances, one of which was Eugene W. Hilgard, professor emeritus of agricultural chemistry at the University of California at Berkeley, who was also his wife's cousin. He also visited and delivered lectures at several other universities, including the University of Chicago.

In 1923, Kossel was honored by being named Germany's representative to the Eleventh Physiological Congress in Edinburgh, Scotland. When he appeared before the assembled Scientists, they gave him an ovation that lasted several minutes. At the congress, he was conferred an honorary degree by the University of Edinburgh.

In 1924, Kossel became professor emeritus, but continued to lecture at Heidelberg University. In April, 1927, he attended the Lister Centenary Celebration held in England.

Luise Kossel died in 1913 of acute pancreatitis. Kossel died quietly on 5 July 1927, after a recurring attack of angina pectoris. He is buried in Heidelberg, Germany.

Albrecht Kossel is considered one of the great Scientists of biochemistry and genetics. By isolating and defining nucleic acid and the nucleobases, he provided the necessary precursors that led to the double-helix model of DNA, devised by James D. Watson and Francis Crick in 1953.