After completing a BFA at Carnegie-Mellon in production design, Wells went through the university's MFA program in directing. Desiring to carry his arts education still further, he enrolled in the Peter Stark Motion Picture Producing Program at USC and received a second MFA in cinema and business law. During this time, Wells worked in marketing and advertising for Paramount Pictures on such productions as "Reds", "Raiders of the Lost Ark", "S.O.B." and "Ragtime" (all 1981) and "One from the Heart" (1982). He also kept active in the theater, producing a number of acclaimed stage productions in L.A., including "Tanzi", "Battery", "Balm in Gilead" and "Steaming". Wells also took an initial stab at feature film producing with the minor yet sometimes engaging, if silly "Nice Girls Don't Explode" (1987).

1987 also marked a breakthrough for Wells into the medium which would gain him the most prominence: several scripts he wrote for the CBS comedy-drama series "Shell Game" were realized. Soon thereafter, he served as executive story editor for the short-term ABC series "Just in Time" (1988) before his first major success in TV with "China Beach" (ABC, 1989-91). Joining the series midway through its run, Wells helped the Vietnam-set drama garner considerable critical acclaim (if not huge ratings). His technical and managerial expertise and sympathy for actors helped him maintain the complex storylines and gritty, detailed realism he has increasingly favored in his work. He set up a production company, John Wells & Friends, which co-produced with Warners TV, his follow-up series, the intriguing and hard-hitting detective saga "Angel Street" (CBS, 1992), but it only lasted for three episodes. Juggling many irons, though, Wells also first ventured into TV-movies with "The Nightman" (NBC, 1992), which he co-executive produced and co-wrote.

Wells' interest in TV and screenwriting would grow through the 90s, gradually combining with his increasing success as a TV producer. He achieved great success with both viewers and critics with his next series, "ER" (NBC, 1994- ), an involving hospital saga which gained considerable respect for its medical detail, its tapestry of complex characters and its avoidance of sugar-coating. "ER" was a hit from the start and in 1995 Wells signed a deal with NBC to develop five more series for the network

After some years away from the cinema, Wells also stretched his time and talents back to one of the few media he had not really conquered. His screenplay biography of one the twentieth century's most remarkable social activists "Entertaining Angels: The Dorothy Day Story" (1996) was produced, but the results were unfortunately little seen. Wells did, however, nail a production deal with DreamWorks SKG around that time, and he also set in motion several projects in development with Warners and Fox. Having worked together with director Mimi Leder on "China Beach" and "ER", the two again collaborated when he served as one of the executive producers of Leder's "The Peacemaker" (1997), starring George Clooney (of "ER" fame) and Nicole Kidman. Wells and Leder teamed up again at DreamWorks as she filmed his screenplay for "Deep Impact" (1998).