Beginning in 1999, Rosenbaum starred in The WB's midseason replacement "Zoe, Duncan, Jack & Jane", a New York City set sitcom often billed as a teen "Seinfeld" because of the exaggerated personality quirks, self-absorption and droll sense of humor incorporated by characters on both series. As Jack, twin of Azura Skye's acerbic Jane, Rosenbaum played a crafty and assured character whose plans are often foiled by his own vanity and cockiness. The actor utilized his sharp delivery and good comic timing as well as a physical presence that belied the awkwardness behind Jack's smug exterior, making the character very realistic and likable, and winning fans with his humorous portrayal. Not on The WB's 1999 fall schedule, the series was revamped to return as a midseason replacement, with the characters aged so that Rosenbaum (one of three twentysomethings in the cast of four playing mid-teen roles) was not quite so much older than the character he was portraying.
The retitled "Zoe" didn't make it past 2000, but Rosenbaum resurfaced on the network in the enviable role of arch villain in training Lex Luthor (complete with shaved head) on "Smallville" (2001- ), The WB's take on Superman's teen years. A conflicted but charismatic rich kid with trauma-related premature baldness he could blame on witnessing the baby of steel's fall to earth, Lex offered Rosenbaum a relatively rich and rewarding role on the hit series.
Rosenbaum returned to the big screen with a supporting role in the 2001 remake of "Sweet November", which briefly featured the actor in drag. He would take that art much further in the 2002 comedy "Sorority Boys", where his Adam and two friends (Harland Williams and Barry Watson) don women's clothing to pledge a sorority in a bid to win acceptance at a fraternity and learn the importance of internal beauty while delivering numerous tasteless punchlines. He made appearances in the comedy feature "Bringing Down The House" as well as the independent film "Poolhall Junkies" (both 2003), in which Rosenbaum portayed a musician who has to choose between his love for music or his love for hustling