Chase struggled with panic attacks and clinical depression as a teenager, something he dealt with into adulthood. He graduated from high school in 1964 and attended Wake Forest University in Winston-Salem, North Carolina, where his depression worsened. “I slept 18 hours a day,” he has stated. He described his problems as “normal, nagging, clinical depression.” He also worked as a drummer during this period and aspired to be a professional musician. After two years, he transferred to New York University where he chose to pursue a career in film—a decision that was not well received by his parents. He went on to attend Stanford University’s School of Film, earning a Master of Arts degree in 1971.

After graduating from NYU in 1968, Chase moved to California and married his high school sweetheart Denise Kelly. He is the father of actress Michele DeCesare who appeared in six of The Sopranos episodes as Hunter Scangarelo.

Chase started in Hollywood as a story editor for Kolchak: The Night Stalker and then produced episodes of The Rockford Files and Northern Exposure, among other series. He also worked as a writer of 19 episodes while on The Rockford Files—a show which he worked on in various capacities for more than four years. He won several Emmy awards, including one for a television movie, Off the Minnesota Strip, the story of a runaway he scripted in 1980. His first original created series was Almost Grown in 1988, with Eve Gordon and Timothy Daly. Although the one-hour series was well received by critics, only 10 episodes aired from November 1988 to February 1989.

Chase worked in relative anonymity before The Sopranos debuted. The story of The Sopranos was initially conceived as a feature film about “a mobster in therapy having problems with his mother”. Chase got some input from his manager Lloyd Braun and decided to adapt it into a television series. He signed a development deal in 1995 with production company Brillstein-Grey and wrote the original pilot script. He drew heavily from his personal life and his experiences growing up in New Jersey, and has stated that he tried to apply his own “family dynamic to mobsters”. For instance, the tumultuous relationship between series protagonist Tony Soprano and his mother Livia is partially based on Chase’s relationship with his own mother. He was also in psychotherapy at the time and modeled the character of Jennifer Melfi after his own psychiatrist.

Chase and producer Brad Grey pitched The Sopranos to several networks; Fox showed interest but passed on it after Chase presented them the pilot script. They eventually pitched the show to Chris Albrecht, president of HBO Original Programming, who decided to finance a pilot episode which was shot in 1997. Chase directed it himself. They finished the pilot and showed it to HBO executives, but the show was put on hold for several months. During this time, Chase, who had experienced frustration for a long period with being unable to break out of the TV genre and into film, considered asking HBO for additional funding to shoot 45 more minutes of footage and release The Sopranos as a feature film. In December 1997, HBO decided to produce the series and ordered 12 more episodes for a 13-episode season. The show premiered on HBO on January 10, 1999, with the pilot, The Sopranos.

Not Fade Away (2012), Chase’s feature film debut, was released on December 21, 2012. It centers on the lead singer of a teenage rock ‘n’ roll band (played by John Magaro) in 1960s New Jersey. Described as “a music-driven coming-of-age story,” the film reunites Chase with James Gandolfini (former star of Sopranos), who co-stars as Magaro’s father. Other cast members include Bella Heathcote, Christopher McDonald, Molly Price, Lisa Lampanelli, Jack Huston and Brad Garrett. Chase himself has described the film as about “a post-war, post-Depression-era parent who has given his kid every advantage that he didn’t have growing up, but now can’t help feeling jealous of the liberated, more adventurous destiny his son is able to enjoy.” Another former Sopranos cast member, Steven Van Zandt, served as music supervisor and executive producer.

Although Chase was “against [the movie] for a long time”, Deadline Hollywood reported in March 2018 that New Line Cinema had purchased the script for The Many Saints of Newark, a prequel to The Sopranos written by Chase and fellow screenwriter Lawrence Konner. Chase said of the storyline, which centers on the 1967 Newark riots and racial tensions between the Italian-American and African-American communities, “I was interested in Newark and life in Newark at that time… I used to go to down there every Saturday night for dinner with my grandparents. But the thing that interested me most was Tony’s boyhood. I was interested in exploring that.” Chase served as producer, and in July 2018, Alan Taylor, who previously directed episodes of the series, was hired to direct the film. The film was initially scheduled to be released on September 25, 2020, however, due to the COVID-19 pandemic in the United States, its release date was rescheduled to March 12, 2021.