Possessing a talent for acting that matched his gift for song, Simmons did well on stage, and climbed through the ranks rather quickly. He made his Broadway debut in 1990's forgettable "A Change in the Heir" but fared better the following year in the dual roles of Captain Hook and Mr. Darling opposite Cathy Rigby in the Broadway and touring revivals of the musical "Peter Pan". A featured role as Benny Southstreet in the acclaimed, long-running revival of "Guys and Dolls" commenced in 1992, punctuated by stints in Neil Simon's "Laughter on the 23rd Floor" (1993) and a multi-character role in the parody "Das Barbecu" (1994).

No stranger to the big screen, Simmons made his feature debut with a turn in "The Ref" and played an assistant coach in the baseball-themed comedy "The Scout" (both 1994). While a quietly commanding supporting role as a major league team manager in the drama "For Love of the Game" (2000) added to his sports feature credits, performances in films including "The First Wives Club" (1996), "The Jackal" (1997), "Anastasia" (1997) and "Celebrity" (1998) showcased a versatile and well-rounded actor. A 1994 guest role on NBC's "Law & Order" marked the beginning of his series television work, but more memorable was his 1996 featured part on an episode of the same network's "Homicide: Life on the Street". His chilling depiction of a self-righteous white supremacist stuck with viewers, as well as with series creator Tom Fontana, presumably, who went on to cast Simmons as Aryan brotherhood leader Schillinger on "Oz".

The role of Vern, which oddly coincided with his portrayal of the exceptionally grounded state psychiatrist Emil Skoda on "Law & Order", offered Simmons the chance to create a multidimensional villain. Schillinger's ferocity in bringing down his enemies was matched only by his instinctive drive to protect his family and his legacy. The character's maniacal yet systematic destruction of archenemy Beecher (Lee Tergesen) was brutal and disturbing, yet in some ways, almost a noble, if obviously wrongheaded, quest. Simmons brought an air of respectability to the character that made the motivation for even his most heinous plots plausible.

Small but memorable parts in films like "The Cider House Rules" (1999), "Autumn in New York" (2000) and "Hit and Runaway" (2001) kept Simmons on the big screen, while a more intensive role as Brad Pitt's criminal mentor and confidante in the comic caper "The Mexican" offered a better opportunity for recognition. Simmons, who had teamed up with Sam Raimi on "For Love of the Game" and 2000's "The Gift", would reunite with the director for the pivotal--and quite amusing--role of the cigar-smoking, Spider-Man-loathing tabloid newspaperman J. Jonah Jameson, who also happens to be Peter Parker's boos, in his friend Sam Raimi's live-action adaptation of "Spider-Man" (2002). Before re-upping as Jameson for an expanded role in the summer sequel "Spider-Man 2" (2004), Simmons was also seen as the legendary Buffalo Bill Cody in the horse race epic "Hidalgo" and as the irritable bowl syndrome-suffering explosive expert Garth Pancake in the Coen brothers' remake of "The Ladykillers" (both 2004). In “Off the Map” (2005), an drama about an eccentric family living on the fringe of society in the New Mexican desert, Simmons played the sole companion of a young girl (Valentina DeAngelis) whose parents have neglected her—dad has been in a deep funk and hasn’t spoken in months, mom prefers to garden in the nude and scavenge junk from the local dump. Directed by Campbell Scott, the film opened to lush reviews, but sparse box office.