Spencer M. Di Scala was born on the lower East side of Manhattan and grew up there and in Queens, New York. He received his B.A. from Queens College (CUNY), New York's public university. His M.A. and Ph.D. degrees are from Columbia University, where he studied under Shepard Clough, A. William Salomone, Peter Gay, Garrett Mattingly, and Eric Goldman. As a graduate student he was awarded two Fulbright grants to Milan, Italy to do research on his dissertation, which later became his first book; and as a professor he won a Senior Fulbright fellowship to Rome to research his second book. Di Scala started teaching at the University of Kentucky and came to UMass Boston in 1970. He has been a full professor since 1986, and in 1997 the university named him research professor. In 2011, he was visiting professor at the Free University in Rome (LUISS) and later in the same year at the University of Rome.

Di Scala's teaching and writing has centered on the history of Italy, with a particular focus on modern Italian Socialism, from which he has branched out into the general history of Italy and modern Europe, to political thought, and to Italian-American subjects. He has taught a range of courses from Western Civilization to advanced courses in Italian and European history of the nineteenth and twentieth centuries, and graduate courses on a variety of specialized topics. In 1995 he was named Commendatore (Commander) in the Order of Merit of the Italian Republic. Di Scala introduced online courses to the history department in 2003 and regularly teaches online and face-to-face courses. In 2006 he won the New England University Continuing Education Association's Award for innovation in teaching and in 2007 UCEA's National Award for Excellence in Teaching.