With his clarion voice and controlled yet energetic acting style, Abel enjoyed considerable success onstage in both leads and character roles in the 1920s. Especially notable were his simultaneous roles in two productions of Eugene O'Neill plays in 1924, "Bound East for Cardiff" and "Desire Under the Elms". He also acted in major productions of "The Enemy" (1925) and "The Seagull" (1928-29), and made his London debut in "Coquette" (1929). Abel played a small film role in Frank Borzage's version of "Liliom" (1930), but his career in movies was not launched in earnest until several years later, by which time he had also performed onstage in New York in "First Mortgage" and "At the Bottom" and on tour in plays including O'Neill's "Mourning Becomes Electra".

Abel's compact size might have seemed a limitation for leading roles in film, but he was signed at RKO in precisely that capacity. His first major effort, though, would later seem a classic case of miscasting: the role of D'Artagnan in one of the many film versions of "The Three Musketeers" (1935). Abel was more than capable of giving a role charm and brio and he tried his best, but the mix of boyish naivete and macho swaggering the role needed simply did not mesh with his looks and acting style. RKO tentatively put him in a few more leading roles in modest programmers like fading diva Ann Harding's swan song for the studio, "The Witness Chair" (1936). Abel was much better served, though, on loan-out to MGM for Fritz Lang's blistering indictment of lynch violence, "Fury" (1936); he was in splendid form as the fiery D.A. who tries an entire mob for its apparent murder of an innocent man (Spencer Tracy).

Often billed as high as second in a cast list, and rarely commanding less than fourth or fifth billing, Abel worked at almost every studio in Hollywood. He was most often cast in modern stories and was rarely the villain. Instead, he played successful but usually modest middle-class businessmen; in comedy Abel could amusingly convey frustration, while in drama he could be quietly helpful or crusading as the occasion demanded. He spent the first half of the 1940s at Paramount; while there he essayed one of his best-remembered roles as the newspaper editor in the offbeat wartime serio-comedy, "Arise My Love" (1940). Supporting Claudette Colbert and Ray Milland as they chase after news, Abel made an indelible impression repeating his key line, "I'm not happy; I'm not happy at all", succinctly summing up his always vaguely dissatisfied Everyman persona.

Abel was also highly amusing in the musical "Holiday Inn" (1942), as Bing Crosby thwarts his efforts to locate Fred Astaire's ideal dance partner based on his memory of only the back of her head. He also shone as one of Bette Davis' admirers in the period soap opera "Mr. Skeffington" (1944), finally telling the vain heroine a few truths about herself. After the war Abel returned to the stage for a time in Dalton Trumbo's "The Biggest Thief in Town" (1949) and "The Wisteria Tree" (1952), Joshua Logan's adaptation of Chekhov's "The Cherry Orchard". During the 50s, though, Abel was vice president of the Screen Actors Guild while Ronald Reagan served as president, and he returned to film roles in "So This Is Love" (1953) and "Raintree County" (1957), among others. In the 60s, Abel served as president of the American National Theater and Academy and performed onstage in "Night Life" (1962) and "The Ninety Day Mistress" (1967). Screen credits continued intermittently as well, from the fine suspenser "Mirage" (1965) right up to his last credit in "Grace Quigley" (lensed 1983; released 1985), giving Katharine Hepburn the same sort of able support he had done for so many others.