He was born Robert John Wagner, Jr. in Cincinnati, Ohio. His parents were Robert John Wagner, Sr., a travelling salesman for a pharmaceutical company, and Helen (née Hohman) Wagner, who was a clerk in a bakery. He had a younger sister, Mary Wagner, and a younger brother, William John Wagner.
Wagner's family moved to Los Angeles when Bob was 12. He began acting at the age of 16, when he was discovered by a talent scout while performing in a high school play. He signed with the William Morris Agency and began appearing in small roles in films and television shows.
Wagner's big break came in 1951 when he was cast in the lead role in the film "With a Song in My Heart". He went on to star in a number of successful films, including "Stars and Stripes Forever" (1952), "The Band Wagon" (1953), "The Eddie Cantor Story" (1953), and "Deep in My Heart" (1954).
Wagner's television career began in the early 1950s, when he appeared in episodes of such shows as "Lux Video Theatre" and "The Colgate Comedy Hour". He had his own television series, "It's Always Jan" (1955–1956), and he also starred in the sitcoms "The Bob Wagner Show" (1957–1958) and "The Robert Wagner Show" (1958–1959).
In the 1960s, Wagner continued to appear in films and television shows. He starred in such films as "Sink the Bismarck!" (1960), "The Longest Day" (1962), "The Great Race" (1965), and "Harper" (1966). He also had a recurring role on the television series "The Saint" (1962–1969).
In the 1970s, Wagner's career began to decline. He appeared in fewer films and television shows, and he often had to take on supporting roles. However, he did star in the successful miniseries "Masada" (1981) and "Sins of the Father" (1984).
In the 1980s, Wagner's career rebounded. He starred in the hit television series "Hart to Hart" (1979–1984) and "Scarecrow and Mrs. King" (1983–1987). He also appeared in a number of successful films, including "Ice Station Zebra" (1968), "The Towering Inferno" (1974), and "The Pink Panther Strikes Again" (1976).
In the 1990s, Wagner continued to appear in films and television shows. He starred in such films as "Dragonfly" (2002) and "Austin Powers in Goldmember" (2002). He also had a recurring role on the television series "Monk" (2002–2009).
Wagner's final film performance was in the 2008 film "The Second Chance". He died of pneumonia on March 18, 2008.
Wagner was married three times. He was first married to actress Natalie Wood from 1957 to 1962. They had one daughter together, Natasha Gregson Wagner. He was then married to actress Marion Marshall from 1963 to 1970. They had two children together, Katie Wagner and Joshua Wagner. He was finally married to actress Jill St. John from 1990 until his death in 2008.
Wagner was a successful actor with a career that spanned over six decades. He starred in over 100 films and television shows, and he was a beloved figure in Hollywood.