He graduated in 1976 from Drake University in Des Moines, Iowa, where he majored in Theater and a minored in Art. He studied a semester at the National Theater Institute at The Eugene O'Neill Theater Center, then moved to New York City. Unable to find acting work, he took Retail jobs and worked as an Illustrator. In 1986, he moved to Jacksonville, Florida, where (from 1986–93) he appeared in local productions at Theater Jacksonville and The Players by the Sea and worked as a Director and Teacher at Flagler College. After several years of differing kinds of work including illustration and teaching, Emerson earned a Master of Fine Arts degree at the University of Alabama in the Alabama Shakespeare Festival acting program.

Upon graduation from the University of Alabama in 1995, Emerson returned to New York City, where he appeared in the annual Alabama Shakespeare Festival showcase.

Emerson landed a starring role in 1997 as Oscar Wilde in Moises Kaufman's critically acclaimed off-Broadway play Gross Indecency: The Three Trials of Oscar Wilde, and then followed up with several other notable stage performances. In 1998, he performed opposite Uma Thurman in an off-Broadway production of Le Misanthrope. In 1999, he played the role of Willie Oban in The Iceman Cometh. He co-starred with Kate Burton in both Give Me Your Answer, Do! and Hedda Gabler.

Emerson is married to Actress Carrie Preston, who plays his fiancée, Grace Hendricks, in Person of Interest. Emerson met Preston while he was performing in a stage production of Hamlet in Alabama. They married in September 1998, and both Emerson and his wife starred in Straight-Jacket (2004).

In September 2001, Emerson won an Emmy Award as "Outstanding Guest Actor in a Drama Series", for playing serial killer william Hinks in several episodes of The Practice. In 2006, Emerson began a guest-star role as Benjamin Linus on the serial drama television series Lost. Emerson was originally set to appear in a small number of episodes, then returned for Season 3 as a main cast member and eventually became a main antagonist of the program. He received an Emmy Award nomination in the "Outstanding Supporting Actor" category in 2007 and 2008 for his work in the third and fourth seasons, respectively. He finally won the award in 2009 after being nominated for his role in the fifth season.

On Lost, Emerson's wife Carrie Preston portrayed Emily Linus (Emerson's character's mother) in the flashback sequences of the episode "The Man Behind the Curtain". The two teamed up again, with Emerson portraying Preston's next-door neighbor, in the film Ready? OK! (2008). Most recently, Preston appeared in several episodes of Person of Interest as Grace Hendricks, the former fiancée of Emerson's character, Harold Finch.

Emerson was nominated in 2009 for a Golden Globe in the "Best Performance by an Actor in a Supporting Role" category. He was nominated for an Emmy for each season in which he was listed in the main cast.

Emerson was set to reunite with former Lost cast member and friend Terry O'Quinn, in a comedy-drama tentatively titled Odd Jobs, by J. J. Abrams. It was expected to start filming by the end of 2010, but further development of the show has been postponed. Emerson joined the cast of another Abrams series, Person of Interest, that debuted in September 2011 on CBS. He played a Billionaire who teams up with a supposedly dead CIA agent to fight crime in New York City.