Born in Santa Monica, California, Webb grew up poor in the Bunker Hill slum section of Los Angeles to a mixed-religion couple, although he was raised Catholic. He was a sickly child and studied art as a young man. One of the tenants in the rooming house run by his mother was an ex-jazzman who imbued Webb with a lifelong interest in jazz when he gave him a recording of Bix Beiderbecke's "At the Jazz Band Ball."

After serving as a crewmember of a B-26 Marauder in World War II he starred in a radio show about a private detective, Pat Novak for Hire. Other radio shows include Johnny Modero—Pier 23, Jeff Regan—Investigator, Murder and Mr. Malone, and One Out of Seven.

Webb had a role in the 1948 film He Walked by Night about the murder of a California Highway Patrolman. The film was made in docudrama style with technical advisors Capt. Harry Didion and Detective Marty Wynn of the Los Angeles Police Department. It was this film that gave Webb the idea for Dragnet. After getting assistance from, and riding along with, Los Angeles police personnel, Webb produced Dragnet which premiered in 1949 on the NBC radio network. Sponsored by Fatima cigarettes, Dragnet starred Webb as Joe Friday and Barton Yarborough as Ben Romero. They played detective sergeants working various divisions. Walter Schumann composed the theme music for the show. Webb narrated the show in first person as the character Joe Friday and maintained almost fanatical attention to detail. Webb believed that viewers wanted "realism" and strove to give it to them. Jack Webb had tremendous respect for the people in law enforcement. He often mentioned in interviews that he was angry about the "ridiculous" amount of abuse that they were often subjected to. He said that he wanted to perform a service for the police by showing them as heroes and perhaps "make their life a little easier".

Despite his reputation, he wasn't above bending the rules, according to one "Dragnet" technical advisor who pointed out that several circumstances in one episode were extremely unlikely. "You know that, and now I know that. But that little old lady in Kansas will never know the difference," Webb said.

In 1950, Webb appeared alongside future Dragnet 1967 partner Harry Morgan in the film noir Dark City.

The year 1951 saw Dragnet become a successful television show. Unfortunately Barton Yarborough died suddenly, and Barney Phillips (Ed Jacobs) and Herbert Ellis (Frank Smith) supplanted his partner. In 1952, Ben Alexander would step in as the jovial, burly Frank Smith. Alexander proved to be a popular addition to the show as Webb's detective partner and remained with it until its cancellation in 1959.

Dragnet began with "The story you are about to see is true. Only the names have been changed to protect the innocent." At the end of each show, the results of the trial of the suspect and severity of sentence were announced by Hal Gibney. Webb frequently re-created entire floors of buildings on soundstages, such as the police headquarters at Los Angeles City Hall for Dragnet and a floor of the Los Angeles Herald-Examiner Building for the 1959 film -30-.

During the early days of Dragnet, he continued to appear in other movies, notably the 1950 Billy Wilder film Sunset Boulevard.

Webb's personal life was better defined by his love of jazz than his interest in police work. His life-long interest in the cornet and racially tolerant attitude allowed him to move easily in the jazz culture, where Webb met singer and actress Julie London. They married in 1947 and raised two children. They later divorced and Webb married three more times.

In 1951, Webb introduced a short-lived radio series, Pete Kelly's Blues, in an attempt to bring the music he loved to a broader audience. That radio series became the basis for a 1955 movie of the same name. However, neither the radio series nor the movie resonated with the audiences of the time. Webb also tried his hand in several other movies that did not gain major status at the box office, such as The DI, a 1957 film about a US Marine Corps drill instructor.

In 1967 Webb produced and starred in a color version of Dragnet for TV. This co-starred Harry Morgan as Officer Bill Gannon. The show's pilot was to air earlier, but was shelved until 1969; the series itself ran through 1970.

Beginning in 1968, in concert with Robert A. Cinader, Webb produced Adam-12 about a rookie and his older partner who patrolled the streets of Los Angeles as uniformed officers Pete Malloy (Martin Milner) and rookie Jim Reed (Kent McCord). The show ran until 1975.

Webb produced The DA with Robert Conrad and O'Hara: US Treasury with David Janssen. These were short-lived, but another show, Emergency!, proved to be a major success, running from 1972 to 1977, and its ratings occasionally even topped its timeslot competitor, All in the Family. Webb cast his ex-wife, Julie London, as well as her second husband and Dragnet regular, Bobby Troup, as nurse Dixie McCall and Dr. Joe Early.

Project UFO was another Webb production and depicted Project Blue Book, a US Air Force investigation into unidentified flying objects. This was the last major product of his Mark VII production company. The end credits for the Mark VII productions famously showed a man's hands using a sledge hammer and plate with the "VII" being engraved into concrete, the hands belonged to Webb.

He considered resurrecting Dragnet in 1983 with Kent McCord as his partner before he died of a heart attack in 1982 at the age of 62. He was interred in the Forest Lawn, Hollywood Hills Cemetery in Los Angeles. Webb was given a funeral with full police honors (including the chief of police announcing that the badge number 714 that Webb used in Dragnet would be retired) although he had never actually served on the force.

Not only did the LAPD use Dragnet episodes as training films for a time, they also named a police academy auditorium after him.

Webb's legendary series (including Dragnet, Adam-12, and Emergency!) are rarely seen today due to the fact that his estate now owns the rights. However, Universal (the original series' distributor) has released many of Webb's series on DVD.