After appearances in a handful of busted pilots, Ferguson garnered attention as amnesia victim Burke Andrew in the Showtime miniseries "Armistead Maupin's More Tales of the City" (1998). That same year, he was seen in the flashback sequences as Lisa Kudrow's brother in the superior "The Opposite of Sex". After completing the indie "The Surprise Party" (lensed 1999), in which he starred as the birthday boy, Ferguson made his US TV debut as a series regular as the uptight lawyer and former husband of a book editor (Susan Floyd) who has begun a relationship with a much younger man in the ABC midseason sitcom "Then Came You" (2000).

Ferguson worked with television director Neill Fearnley on a pair of nostalgic, music-minded TV biopics: "Daydream Believers: The Monkees Story" (VH1, 2000), with Ferguson playing the fictionalized character Van Foreman (likely a composite of film director Bob Rafelson and producer Bert Schneider); and "Inside the Osmonds" (ABC, 2001), with Ferguson playing real-life recording executive Mike Curb. He next appeared as Dr. Witt in the much-praised HBO film "We Were the Mulvanys" (2002) based on the well-known Joyce Carol Oates novel, opposite Beau Bridges and Blythe Danner. The actor would at last have his opportunity to become a household name when he was cast as charismatic, cocky Patrick Bateman, the king of conquest amide the sexed-up sextet in NBC's "Coupling" (2003- ), an Americanized version of the hit BBC comedy that was touted as the Must-See TV successor to the departing "Friends."