A veteran of vaudeville and Broadway-level stage productions, Portland Hoffa met Fred Allen while performing in The Passing Show in 1922 and joined him in his vaudeville routines (centered around his clever jokes spun off his weakness as a juggler); the couple married before Allen began his long-running radio work in 1932, with Hoffa taking instruction in the Roman Catholic Church prior to the marriage.
Hoffa became familiar for her high-pitched voice, her brief routines involving jokes bounced off or from her mother, and, later, strolling Allen's Alley with her husband, after asking him what his question of the week for the Alley denizens would be. Although Hoffa performed under her real name on her husband's show, the character she portrayed as "Portland Hoffa" in the radio broadcasts was not Allen's wife; instead, she depicted an enthusiastic girl of indeterminate age, around thirteen years old. One of Allen's sponsors loathed the character played by Hoffa, and kept urging Allen to drop her from the show. Allen ignored these requests for as long as he could, then finally — in an angry outburst at a sales meeting — told the executive that the broadcasts were bearable only due to Hoffa's presence, and that if she were removed from the program then Allen would quit.
Fred Allen's declining health was the main reason why he ceased hosting his own show after 1949, but Hoffa often joined him as a semi-regular on Tallulah Bankhead's radio variety show, The Big Show (1950–52). She also appeared as the "mystery guest" on one episode of television's What's My Line, on which Allen had become a panelist from 1954 until his death in early 1956. Hoffa and Allen had also appeared in such films as Is Everybody Listening? (1947) and the Jack Benny vehicle Buck Benny Rides Again (1940).
Hoffa re-married in 1959, to bandleader Joe Rines, later an advertising executive. Hoffa and Rines lived long enough to celebrate a silver wedding anniversary, allowing Hoffa an unusual second such anniversary in one lifetime. In 1965, Hoffa rounded up a large volume of her first husband's correspondence to be edited into Fred Allen's Letters. Rines died in 1986. Like her first husband, Portland Hoffa has a star on the Hollywood Walk of Fame. Hoffa died of natural causes in 1990.