Mario Renato Capecchi is born in 1937 in Verona, Italy to Lucy (née Ramberg) and Luciano Capecchi. His mother is imprisoned by the Nazi regime and his father is abusive and does not take care of him. After living on the streets and orphanages during the war years he is reunited with his mother in 1946 and both move to the United States.

Mario Capecchi attends Antioch College to study Political Science. However he soon changes to physics and chemistry. Capecchi receives his B.S. degree in 1961.

Mario Capecchi lives with his aunt and uncle in Pennsylvania. He attends George School, a Quaker school. There he particularly enjoys athletics.

Mario Capecchi, Martin Evans and Oliver Smithies create the first 'knochout mouse'. They genetically modify a mouse by replacing an existing gene with artificial DNA. This changes the phenotype of the animal and includes changes in appearance, behaviour and other physical and biochemical characteristics. The technology allows scientist to evaluate in detail the function of any gene.

Mario Capecchi attends Harvard University and studies molecular biology under James D. Watson. Capecchi generates a cell-free extract capable of synthesizing real functional proteins. He uses a similar mechanism to show that the termination of protein synthesis unexpectedly utilizes protein factors, rather than tRNA. Capecchi receives his Ph.D. in 1967.

Mario Capecchi enters the University of Utah. Since 1993 he is Professor of Human Genetics and Biology. His reserach interests include neural development in mammals, molecular genetics, gene therapy and homologous recombination and programmed genomic rearrangements in mice.

Mario Capecchi joins the faculty in the Department of Biochemistry at Harvard Medical School and serves as an Assistant Professor. Because the research groups are working rather seperately Capecchi decides to leave Harvard.

Mario Capecchi marries Laurie Fraser. They have one daughter.

As part of a work-study program Mario Capecchi joins the Massachusetts Institute of Technology. He becomes interested in molecular biology and works at Alex Rich's laboratory, specifically on x-ray crystallography.

Mario Capecchi, Martin Evans and Oliver Smithies are awarded the Nobel Prize in Physiology or Medicine in 2007 for their discoveries of principles for introducing specific gene modification in mice by the use of embryonic stem cells.