In December 2012, Watkins had twins, Catchen (Catch) and Curtis, via a surrogate named Melissa.
Watkins started his career with guest appearances on various television series including Sisters (three episodes from 1991 to 1992), Baywatch ("Game of Chance", 1992), and Melrose Place ("Single White Sister", 1993). He portrayed con-man David Vickers on the ABCsoap operaOne Life to Live from 1994 to 1996, next joining the soap opera General Hospital in the recurring role of Dr. Pierce Dorman from 1996 to 1997. Watkins went on to star as Malcolm Laffley on the Showtime series Beggars and Choosers for its two-season run from 1999 to 2001. In 1999, he made his film debut in I Think I Do, a small budget independent screwball romantic comedy, playing Sterling Scott, the soap opera hunk boyfriend of Bob, played by Alexis Arquette. He followed this with his first appearance in a big studio production, The Mummy as the near-sighted glasses-wearing tomb raider Burns, later guest-starring on television series such as NYPD Blue ("The Irvin Files", 2000), Six Feet Under ("Out, Out, Brief Candle", 2002), and CSI: Crime Scene Investigation ("Cats in the Cradle...", 2002). After brief appearances in 2001 and 2002, Watkins rejoined the cast of One Life to Live full-time from 2003 through 2006, with several short term returns to the show in 2007, 2008, and 2009, returning again on a regular basis beginning in June 2010.Soap Opera Digest named Watkins's David their "Most Entertaining Male Character" of 2008, noting that "Time and time again, David's harebrained schemes and Tuc Watkins's side-splitting performances provide amusement we're always sorry to see end."
On October 21, 2007, Watkins made his first appearance on ABC's prime time series Desperate Housewives as Bob Hunter, a new resident of Wisteria Lane who is a gay lawyer with a husband. On November 4, 2007 Watkins guest-starred on the Cold Caseseason 5 episode "World's End". In July 2009, a Funny or Die video called The Sentimentalist starring Watkins was ranked #5 on Entertainment Weekly's "The Must List", which notes the magazine's ten weekly choices among film, television, DVDs, books, music, and online entertainment for "The Top 10 Things We Love This Week".
Tuc Watkins joined the cast of Desperate Housewives as a series regular.
1994 - 1996: One Life to Live as David Vickers (Role since: 1994 - 1996, October 2001, January 2002, August 2003 - November 2006, March 6, 2007, May - July 26, 2007, November 2007, May 7 - August 6, 2008, December 26, 2008 - March 2, 2009, April 7, 2009, April 22–27, 2009, August 10, 2009, June 3, 2010–January 12, 2012, April 29, 2013 – present)