The series began as four TV movies broadcast in Spring 1977, and their high ratings led NBC to commission a weekly series for the 1977–78 season.

Despite the high ratings of the TV movies, the weekly series was cancelled after only 13 episodes due to a declining audience and high production costs.

Actress Belinda J. Montgomery, who played Dr. Elizabeth Merrill, felt her character was increasingly sidelined as the scripts grew sillier, and she managed to get out of her contract with the help of lawyers after 11 episodes.

Producer Herbert Solow cast his then-wife Pamela Peters Solow, twenty years his junior, in two different roles in the show—first in the TV movie 'The Disappearances' and later in the episode 'C.W. Hyde'—both times billing her prominently as 'and Pamela Peters Solow as...' despite her being a relative unknown.

The weekly series shifted tone toward escapist fantasy reminiscent of Star Trek, with Mark as an adventurer captain of the submarine Cetacean similar to Captain Kirk; this connection is notable since producer and co-creator Herbert Solow had also helped bring Star Trek to television in the 1960s.

The Foundation for Oceanic Research headquarters was represented on screen by the real Point Fermin lighthouse in San Pedro, California.

The Cetacean submarine's voyages were realized through miniature work by special effects artist Gene Warren, and the series introduced a new Seabase set with a moving cradle and enclosed walkway to avoid having to film diving and surfacing effects.

Man from Atlantis was the first American television series ever shown in the People's Republic of China, debuting on March 1, 1980, and became so popular that a foreign pianist's concert start time had to be rescheduled around its broadcast.

In the United Kingdom, the series aired opposite the BBC's Doctor Who in its 15th season and actually beat it in the ratings, despite not being a ratings success in the United States.

Kenner Toys developed a Man from Atlantis action figure line in 1977 but it never went beyond the prototype stage, while British company Denys Fisher Toys reportedly passed on making UK Star Wars action figures because they believed Man from Atlantis merchandise would sell better.

In 2016, series star Patrick Duffy wrote and published his own sequel novel titled Man from Atlantis, presenting his personal take on the mythology and origins of Mark Harris and Atlantis.