Elizondo made his film debut (fully clothed) in the sexploitation film "The Vixens" (1969), and has since proved as comfortable switching ethnic identities as he has changing the many wigs that he sometimes uses to cover his natural baldness. He played the police officer who takes lessons in dressing from Richard Gere in "American Gigolo" (1980) and is a favorite of director Garry Marshall, who has cast him in diverse roles like Angelo and Angela Bonafetti in "Young Doctors in Love" (1982); Matt Dillon's sympathetic working-class father in "The Flamingo Kid" (1984); Tom Hanks' ad agency boss in "Nothing in Common" (1986); and Julia Roberts' fairy godfather--in the form of a supportive hotel manager--in "Pretty Woman" (1990).
In 1991, Elizondo completed his fifth cinematic collaboration with Marshall, the 50s style "working-class" love story "Frankie and Johnny", in which the played the warm and cheap Greek owner of a greasy spoon. Although Marshall has made a couple of films without the actor, his billing in Marshall's rather mild farce set at a sex resort, "Exit to Eden" (1994) listed him as "Hector Elizondo, of course". Now considered Marshall's good luck charm, additional roles in "Dear God" (1996), "The Other Sister" and "Runaway Bride" (both 1999), "The Princess Diaries" (2001) plus its sequel "Princess Diaries 2: Royal Engagement" (2004), and "Raising Helen" (2004) followed. He also headlined the Latin-flavored "Tortilla Soup" (2001), a loose reworking of Ang Lee's 1994 feature "Eat Drink Man Woman".
The actor remained busy on the small screen as well, starring, for example, as Sandy Stern in the TV miniseries "The Burden of Proof" (1992), adapted from the Scott Turow novel. He also had the key role as hospital administrator Dr. Watters on the long-running CBS medical drama drama "Chicago Hope" (1994-2000) throughout the run of the series, for which he earned a supporting actor Emmy in 1997. After that series ended he continued to remain in demand, appearing in a string of short-lived series that failed to catch on with viewers, including "Kate Brasher," "Miracles" and "Century City." Elizondo also had a supporting turn in the well-regarded Showtime miniseries "Fidel" (2002).