Bradley Walsh similarly played an evil entity that appeared in various guises as a clown (named Odd Bob), a ringmaster (named Elijah Spellman) and the Pied Piper in The Sarah Jane Adventures, more recently playing a Companion in the main DW series.
Odd Bob was creepy af, as I remember it - not just because he was a clown but the accent, quiet but intense mode of speaking and strange head tilt.
Joseph C. Phillips first played a date of the oldest daughter on the Cosby Show, then came back a few seasons later as the husband of the next oldest daughter (Lisa Bonet)
Speaking of a strange one from Law & Order ---- Jeremy Sisto played lawyer Clint Glover in the last episode of season 17 only to return in the first episode of season 18 as Det. Cyrus “Lupes” Lupo.
Another Law & Order one – Michael Imperioli had a part in a 1996 episode, and came back in 2006 to play Det. Nick Falco in several episodes.
To hijack the thread a bit, Law & Order had so many actors in guest roles who played continuing characters on The Sopranos that the A&E network once had a L&O marathon where each episode included a Sopranos actor.
Jonathan Pryce appeared in a 1981 production of Harold Pinter’s The Caretaker as Mick, then in a 2012 production as Davies.
Midsomer Murders has too many names to list.
So do the original Mission: Impossible and Hawaii Five-O.
I don’t think this is quite what the OP is looking for, but A&E’s Nero Wolfe series had two regular characters, Maury Chaykin as Nero Wolfe and Timothy Hutton as Archie Goodwin, a half dozen actors playing recurring characters, and then a dozen or so actors in a repertory pool. The repertory actors each appeared in several episodes, each time as a different one-off character.
A bit more on-point for the OP, Saul Rubinek played a one-off character in the pilot, then came back in several episodes as a different recurring character. Kari Matchett played both a recurring character, Lily Rowan, Archie Goodwin’s on-and-off girlfriend, and several one-off characters, often women who had or feigned a romantic interest in Archie. She even played Lily Rowan and a different one-off character in the same episode!
(Total tangent: In a nice bit of stunt casting, she also played the ex-wife of Timothy Hutton’s character in a couple of episodes of the later series, Leverage).
One of us is confused… I thought the other characters were named “Zathras” and “Zathras”, not “Zathras”.
But if we’re talking Babylon 5, then the winner has to be Wayne Alexander, who played at least five different characters ove r the course of the show, none of whom were “twin brothers” or anything like that.
And another science fiction one, with major roles: Richard Hatch played Apollo in the original Battlestar Galactica, then came back to play Tom Zarek in the 2003 version.
“Zathras have very sad life. Probably have very sad death. But, at least there is symmetry.”
Of course, there are always actors like Janos Prohaska…
Prohaska also appeared in multiple roles on such TV series as The Outer Limits , Bewitched , I Dream of Jeannie , Lost in Space , and a few episodes of Gilligan’s Island , where he plays a gorilla. On NBC-TV’s Star Trek his turns as the Horta in Star Trek’ s “The Devil in the Dark”, and the Mugato (credited, curiously enough, as the Gumato) in “A Private Little War” are the best known of these.
Technically it hasn’t happened yet, but Patrick Stewart in the 1984 Dune movie plays Gurney Halleck, while in the 2021 version will play the Emperor.
John Wesley Shipp played Barry “The Flash” Allen in the ‘90s TV show — and, decades later, they had him field a recurring role as Barry‘s wrongfully-convicted physician father Henry Allen in the version that’s on now; and, since it’s The Flash, with guys so fast they can zoom back in time or vibrate over to parallel timelines, they eventually (a) had Shipp suit back up as his ‘90s incarnation, and also (b) had him suit up as another world’s Jay Garrick.
Columbo had multiple actors who reappeared as different characters. Patrick McGoohan was the most prolific, as four different muderers on his appearances.
Suzie Plakson played Ambassador K’Ehleyr and Dr. Selar in Star Trek: TNG, and then played a Female Q on ST: Voyager and an Andorian on ST: Enterprise.
Not sure whether this counts but…
Actor John Mahoney played a songwriter in an episode of Cheers. He played the father of Frasier (and Niles) Crane in the spin off Frasier.
TCMF-2L
NYPD had Currie Graham play a guy who got arrested and later he played the leader of the 15th Det squad
Dean Cain played Clark Kent in Lois & Clark and later Jeremiah Danvers (Kara’s adoptive father) on Supergirl.
On Gunsmoke, Ken Curtis played a few different characters in several episodes before he started to play Festus. Buck Taylor appeared in one episode playing a different character before he started to play Newly.
Similarly, Helen Slater played Supergirl in the 1984 film, and later Eliza Danvers (Kara’s adoptive mother) in the television series. Clever casting there.
Teri Hatcher (who played Lois against Cain’s Clark) also had a guest villain role in the Supergirl series.
Charlton Heston played Taylor, the lead character in the 1968 version of Planet of the Apes. He played Zaius in the 2001 remake. (Linda Harrison, who played Nova in the original, also had a cameo appearance in the remake.)