Updated: February 18, 2022

As Doctor Zachary Smith in Lost in Space:

Harris as Dr. Zachary Smith Harris beat out two other actors for the role of conniving, cowardly agent Dr. Zachary Smith on Lost In Space for CBS. The character did not appear in the original 1965 pilot episode (nor did The Robot). The series was already in production when he joined the cast and the starring / co-starring billings had already been contractually assigned, so Harris received a "Special Guest Star" credit on every episode.

A strong bond developed between Harris, Mumy, and some of the rest of the cast during the show's three-year tenure. From its debut, it was an immediate hit, even though midway through the first season, it had competition from another newcomer, Batman, which dominated the ratings. The show continued the tradition of such successful 1960s sci-fi series such as Voyage to the Bottom of the Sea. Midway through the first season, due to Harris' popularity on the show, he began to rewrite the dialogue. Allen approved his changes and gave him carte blanche to become a writer. Harris stole the show, mainly via a list of alliterative insults that soon worked their way into popular speech. When the show was renewed for its third and final season, it remained focused on Harris's character, Dr. Smith. While the series was still a big hit, the writers appeared to run out of fresh ideas, and the show was unexpectedly canceled in 1968, after 83 episodes.

One of Harris's co-stars, Mark Goddard, said of the show's eventual shift toward Harris's character, "I guess it was because they felt that the people wanted to see more of the Robot and Jonathan. Originally, when it was more science fiction, Irwin can really do those things so beautifully. So he really took those away from himself when he wanted to deal with the Robot and Jonathan playing games, cooking souffles, or whatever else," Goddard also added if he had gotten along real well with other castmates, other than Harris & Mumy, "No. There was a lot of tension on the set for the three years it was filmed. There was always a lot of tension, because the shows started going more toward the Robot and Smith. There were hard feelings from especially Guy and June, and also myself, but not as heavy as them, because they were originally sold as being the stars of the show when it began. It ended up that Harris became the star of the show," the last thing that he said, "I was friendly with everyone, pretty much. I think there was a period for a couple of months when I was angry at Jonathan Harris, for the same reasons, feeling that he was getting too many shows thrown his way. But we talk today. I see him, and there's no animosity between us. But I also had my disagreements with Guy Williams. When they started taking shows away from Guy, giving more to Jonathan, then Guy would come in and demand whatever I had in the show: any confrontations with Smith, or to save the kid, or anything. He'd end up doing all of that and I was the one that got squeezed out; I was doing almost nothing. There was one time where I went in to do a bit and had learned my lines, and was all ready to do my scene, when Guy started reading my lines. I said 'What's going on?' and he said 'This is my scene now.' They had given the lines to him. And that's where I got angry and walked off."

After the show went off the air, Goddard had graduated from the being a series' co-star to the more professional actor of stage, who in turn, also went back to his native Massachusetts, in becoming a certified Special Education teacher. When on hiatus, he realized that on June 14, 1995, Goddard was also reunited with the entire surviving Lost in Space cast to pay tribute to Irwin Allen who died late in 1991. He even appeared with the cast of Lost in Space on the front cover of TV Guide to promote the new movie, at the same time the Sci Fi Channel would feature a Lost in Space marathon. In the actual 1965 television premiere of "Lost in Space", the blast off of the Jupiter-2 is set in the future on October 16, 1997. The Sci-Fi Channel began the "Lost in Space" marathon in real-time 32 years later on October 16, 1997, all this took place, after Sam's death in 1977, at the time the relationship between Harris & Goddard drew much closer. He continued to stay in touch with Harris until his friend's death, late in 2002.

Bill Mumy said about Harris' guest role that in his first episode, "It was actually implied that this villainous character that sabotaged the mission and ended up with us, was going to be killed off after a while." Mumy added, "Jonathan played him as written, which was this really dark, straight-ahead villain, who was trying to murder women and children." Mumy also said of Harris's work on Space, "And we'd start working on a scene together, and he'd have a line, and then in the script I'd have my reply, and he'd say, 'No, no, no, dear boy. No, no, no. Before you say that, The Robot will say this, this, this, this, this, this, and this, and then, you'll deliver your line.'" Bill also said of Harris' portrayal, "He truly, truly singlehandledly created the character of Dr. Zachary Smith that we know this man, we love-to-hate, coward who would cower behind the little boy, 'Oh, the pain! Save me, William!' That's all him!" About the show's cancellation, Mumy said, "I don't know what happened. All I know is that we were all told we're coming back. Then, you know we got a call that we weren't." The death of Harris' father in 1977 drew Harris and Mumy closer. The two kept in touch for almost 35 years until Harris' death.

On June 14, 1995, Mumy & the rest of the crew paid tribute to series' creator Irwin, who died late in 1991. In 1996, Mumy was reunited with Harris alongside Leonard Nimoy (of Star Trek fame), at a Disney World convention. It was also reported in 1997 that Mumy, Harris and the rest of the surviving cast appeared on the inside cover of TV Guide to promote the new movie, while the Sci-Fi Channel would feature a Lost in Space marathon. In the actual 1965 television premiere of "Lost in Space", the blast off of the Jupiter-2 is set in the future on October 16, 1997. The Sci-Fi Channel began the "Lost in Space" marathon in real-time 32 years later on October 16, 1997.