Perl was born in New York City, New York. His parents, Fay (née Resenthal), a secretary and bookkeeper, and Oscar Perl, a stationery salesman who founded a printing and advertising company, were Jewish emigrants to the US from the Polish area of Russia.

Perl is a 1948 chemical engineering graduate of Brooklyn Polytechnic Institute (now known as NYU-Poly) in Brooklyn. After graduation, Perl worked for the General Electric Company, as a chemical engineer in a factory producing electron vacuum tubes. To learn about how the electron tubes worked, Perl signed up for courses in atomic physics and advanced calculus at Union College in Schenectady, New York, which led to his growing interest in physics, and eventually to becoming a graduate student in physics in 1950.

He received his Ph.D. from Columbia University in 1955, where his thesis advisor was I.I. Rabi. Perl's thesis described measurements of the nuclear quadrupole moment of sodium, using the atomic beam resonance method that Rabi had won the Nobel Prize in Phyics for in 1944.

Following his Ph.D., Perl spent 8 years at the University of Michigan, where he worked on the physics of strong interactions, using bubble chambers and spark chambers to study the scattering of pions and later neutrons on protons.[1] While at Michigan, Perl and Lawrence W. Jones served as co-advisors to Samuel C. C. Ting, who earned the Nobel Prize in Physics in 1976.

Seeking a simpler interaction mechanism to study, Perl started to consider electron and muon interactions.[2] He had the opportunity to start planning experimental work in this area when he moved in 1963 to the Stanford Linear Accelerator Center (SLAC), then being built in California. He was particularly interested in understanding the muon: why it should interact almost exactly like the electron but be 206.8 times heavier, and why it should decay through the route that it does. Perl chose to look for answers to these questions in experiments on high-energy charged leptons. In addition, he considered the possibility of finding a third generation of lepton through electron-positron collisions.