Loggia was a radio and TV anchor in Southern Command Network in the Panama Canal Zone. Loggia first came to prominence playing real-life American lawman Elfego Baca in a 1958 series of Walt Disney television shows. He starred as the proverbial cat-burglar-turned-good in a short-lived series called T.H.E. Cat. In 1972 he played Frank Carver on the CBS soap opera The Secret Storm. His many television credits include appearances on Frasier, Overland Trail, Target: The Corruptors!, The Eleventh Hour, Breaking Point, Combat!, Custer, Columbo, Ellery Queen, Starsky and Hutch, Charlie's Angels, The Rockford Files (three times as three different characters), Magnum, P.I., Quincy ME, The Sopranos, Monk, Oliver Stone's miniseries Wild Palms and Little House on the Prairie.
His film roles include An Officer and a Gentleman, Mercy Mission: The Rescue of Flight 771, based on the Air New Zealand Flight 103 incident, Scarface, Prizzi's Honor, Over The Top, Independence Day, Necessary Roughness, Return to Me, Armed and Dangerous, and Big (for which he won a Saturn Award for Best Supporting Actor).
In 1985, Loggia was nominated for an Academy Award for Best Supporting Actor for his portrayal of crusty private detective Sam Ransom in the thriller Jagged Edge. He was nominated for an Emmy in 1989 for his portrayal of FBI agent Nick Mancuso in the TV series Mancuso, FBI, a follow up to the previous year's miniseries Favorite Son. Loggia appeared as mobsters in multiple films including Sykes in Disney's Oliver & Company (1988), Salvatore 'The Shark' Macelli in John Landis' Innocent Blood and Mr. Eddy in David Lynch's Lost Highway (1997) and The Don's Analyst (1997).
In 1998, Loggia appeared in a television commercial lampooning obscure celebrity endorsements. In it, a young boy names Loggia as someone he would trust to recommend Minute Maid orange-tangerine blend; Robert Loggia instantly appears and endorses the drink, to which the boy exclaims, "Whoa, Robert Loggia!" The commercial was later referenced in an episode of Malcolm in the Middle in which Loggia made a guest appearance as "Grandpa Victor" (for which he received his second Emmy nomination); Loggia drinks some orange juice, then spits it out and complains about the pulp. In a similar vein, Loggia has been parodied on an episode of the show Family Guy titled "Peter's Two Dads." Loggia also played a violent mobster named Feech La Manna on a few episodes of the series The Sopranos.
In addition to his role in Oliver & Company (1988), Loggia has had several other voice acting roles. A recurring role on the Adult Swim animated comedy Tom Goes to the Mayor, as crooked cop Ray Machowski in the video game Grand Theft Auto III, as Admiral Petrarch in FreeSpace 2, as the narrator of the Scarface: The World is Yours game adaptation, and in the anime movie A Dog of Flanders (1997).
In August 2009, Loggia appeared in one of Apple's Get a Mac advertisements. The advertisement features Loggia as a personal trainer hired by PC to get him back on top of his game.
On October 26, 2009, TVGuide.com announced Loggia joined the cast of the TNT series Men of a Certain Age. The role had him teaming up again with his Necessary Roughness co-star Scott Bakula.
In 2010, he was awarded the Ellis Island Medal of Honor in recognition of his humanitarian efforts.