Tyler Hoechlin and Elizabeth Tulloch star as the title characters Clark Kent / Superman and Lois Lane, respectively.

The series also stars Erik Valdez, Inde Navarrette, Wolé Parks, Adam Rayner, Dylan Walsh, Emmanuelle Chriqui, Tayler Buck, Sofia Hasmik, Chad L. Coleman, and Michael Cudlitz.

The series was originally part of the Arrowverse's Earth-Prime in its first season, developed as a spin-off of Supergirl, with Hoechlin and Tulloch respectively reprising their roles from Supergirl and The Flash (and the conclusion of the "Crisis on Infinite Earths" crossover event serving as a backdoor pilot), but as the series went on, following the cancellation of planned crossovers with Supergirl and Batwoman due to the COVID-19 pandemic, showrunner Todd Helbing and Warner Bros. decided to keep the show separate, with the series instead set in its own separate continuity taking place on a different Earth to the Arrowverse's Earth-Prime, which was confirmed in the second season finale.

In the first season, Clark Kent / Superman and Lois Lane return to Smallville with their sons Jonathan and Jordan, where they are reacquainted with Lana Lang, her husband Kyle Cushing, and their daughter Sarah.

[1] In the second season, Superman's painful visions lead him to an encounter with Bizarro while also butting heads with Lt. General Mitch Anderson.

Meanwhile, Lois deals with the Inverse Method cult led by Ally Allston, who swayed Lucy Lane to her side and has made an enemy of Bizarro for her supposed conquering of his world.

In the third season, Superman contends with the plots of Intergang, as Lois suffers from stage three inflammatory breast cancer.

In the fourth and final season, Superman continues his fight with the mutated Bizarro, known as Doomsday, as Luthor begins his next plot that involves setting up a new base where the Manning Farm is.

[79] In January 2023, DC Studios CEOs James Gunn and Peter Safran said they expected the show to continue for "one to two more seasons".

[84] Tyler Hoechlin and Elizabeth Tulloch were signed on to reprise their roles as Clark Kent and Lois Lane from Supergirl.

[11] In October 2020, Sofia Hasmik and Stacey Farber were cast in the recurring roles of Chrissy Beppo and Leslie Larr, respectively.

[18][85] In December 2020, David Ramsey was revealed to be reprising his Arrow role of John Diggle in addition to directing at least one episode in the series.

[19] Lex Luthor appears in the show where he is now portrayed by Michael Cudlitz instead of a reprisal from Jon Cryer, who played his doppelgänger on Earth-Prime.

[89] Seven of the twelve cast members were cut as series regulars following the renewal of the show for the fourth and final season.

These included Dylan Walsh, Emmanuelle Chriqui, Erik Valdez, Inde Navarrette, Wolé Parks, Tayler Buck and Sofia Hasmik.

[102] Filming for the fourth season began on January 11, 2024 and concluded on April 24, 2024 with Hoechlin receiving a supportive letter from upcoming Superman actor David Corenswet as production wrapped up.

[108] In November 2020, series writer Nadria Tucker announced she was fired from the show, claiming it was for "pushing back on racist and sexist storylines."

[132] The website's critical consensus reads "Though it may be a bit too grounded for some viewers, Superman & Lois draws strength from unexpected places – without skimping on the action – to carve its own path in a crowded superhero universe."

Earth-Prime #2 features Superman & Lois, written by Adam Mallinger, Jai Jamison and Andrew Wong with art by Tom Grummett and Norm Rapmund and was released on April 19, 2022.