The son of a song and dance man who worked in vaudeville and performed on the Broadway stage, Patrick Harrington Jr. pursued a career in entertainment after graduating from Fordham University. Harrington served with the United States Air Force during the Korean war then after being discharged, he took a job at NBC in New York City. He began acting on stage and toured North America with a number of plays and eventually performed on Broadway.

Harrington became famous in the 1950s as a member of Steve Allen's TV comedy troupe, the "men on the street" (which also included Don Knotts, Tom Poston and Louis Nye). Harrington also gained considerable recognition for his many appearances as the comedic Italian immigrant "Guido Panzini" on the Jack Paar Show in the mid 1950s and in 1967 he appeared in the Elvis Presley film, Easy Come, Easy Go.

However, he is best known to later generations for his role as "Dwayne F. Schneider" on the popular 1975-1984 television drama/comedy, One Day at a Time for which he won an Emmy Award and a Golden Globe Award.

Since the end of the successful series, Harrington has worked in film and television, sometimes as a voice actor (The Inspector).