In 2003, Lynskey played a writer for The New Republic in Shattered Glass, a film based on the career of former journalist Stephen Glass.
Jeff Otto of IGN called it "a tension-filled drama with great performances".
Later that year, she landed the part of Rose, the devious but lovable neighbor of Charlie Harper (played by Charlie Sheen) on the CBS sitcom Two and a Half Men.
After initially appearing in the pilot episode as a guest character, Lynskey was invited to become a series regular and went on to appear frequently throughout the show's first two seasons.
Despite leaving the main cast in 2005 to concentrate on film work, she continued to make guest appearances on the show up until its final episode, which aired in February 2015.

Honestly, doing three or four episodes a year enabled me to pay my mortgage and do independent films.
I had this double life: I had this whole indie side of my career, and people in that world didn't know I was on this huge sitcom.
Then, people would recognize me from Two and a Half Men and think that I never had another job.
But I couldn't have done one without the other.

— Lynskey, November 2016
In 2006, Lynskey appeared as the wife of Rene Gagnon in the Clint Eastwood-directed war film Flags of Our Fathers.
Writing for the Honolulu Star-Advertiser, Burl Burlingame called it "the richest testament Hollywood has yet made about the paroxysm of World War II ... an astounding movie on every level".
The following year, she played one of the principal characters—a woman desperate to get away from her abusive husband—on the short-lived television series Drive, which was cancelled by FOX midway through its first season run.
In her review for the Los Angeles Times of the series' first two episodes, Mary McNamara described Lynskey as "especially compelling".

In 2008, Lynskey had a supporting role in the three-part Western miniseries Comanche Moon, which aired on CBS.
The series received mixed reviews from critics, but People commented that Lynskey's performance was among the "best" in the cast.
Later that year, she returned to New Zealand to star in the romantic drama Show of Hands, for which she earned a nomination for Best Actress at the Qantas Film and Television Awards.

Lynskey received strong reviews in 2009 for Away We Go, a comedy-drama directed by Sam Mendes in which she played a woman who has suffered a series of miscarriages.
Wesley Morris of The Boston Globe called it "the best performance in the movie".
Next, she co-starred as Matt Damon's wife, Ginger, in Steven Soderbergh's dark comedy The Informant!.
The film—which is based on real events—was described as "devilish fun" by Rolling Stone, while Geoffrey Macnab said that Lynskey provided "sterling support" in his review for The Independent.
Soderbergh told the Los Angeles Times, "She is so watchable.
You never quite know what you're going to get, you just know it's going to be good.
Her rhythms are really unusual, like her cadence and her reaction times to things, and the way she sort of lays out a sentence.
It's just really, really interesting".
While making the film, Soderbergh discouraged Lynskey from contacting the real person on which her character was based, as he wanted her to reach her own conclusion about whether Ginger had been involved in her husband's crimes. "
I decided she had no idea what was going on", she later said. "
She was trusting, she was the kind of wife who thinks her job is to stay in the house and take care of the kids ... even though some things didn't necessarily add up ... She wasn't asking too many questions".
Lynskey counts her time working on The Informant!
as one of her favorite experiences.

Matt Damon said something to me that I really have lived by ever since ... “At the end of your career, when someone looks over your filmography, all they remember is if the movie was good or not.
They’re not saying, ‘Oh, he [played] that crazy character!’ [
or] ‘Oh, all those people were in that movie’ ... all people know is if the movie was good or not” ... so, if you consistently choose good scripts ... you’re going t
In 2003, Lynskey played a writer for The New Republic in Shattered Glass, a film based on the career of former journalist Stephen Glass. Jeff Otto of IGN called it "a tension-filled drama with great performances". Later that year, she landed the part of Rose, the devious but lovable neighbor of Charlie Harper (played by Charlie Sheen) on the CBS sitcom Two and a Half Men. After initially appearing in the pilot episode as a guest character, Lynskey was invited to become a series regular and went on to appear frequently throughout the show's first two seasons. Despite leaving the main cast in 2005 to concentrate on film work, she continued to make guest appearances on the show up until its final episode, which aired in February 2015.
Honestly, doing three or four episodes a year enabled me to pay my mortgage and do independent films. I had this double life: I had this whole indie side of my career, and people in that world didn't know I was on this huge sitcom. Then, people would recognize me from Two and a Half Men and think that I never had another job. But I couldn't have done one without the other. 
— Lynskey, November 2016
In 2006, Lynskey appeared as the wife of Rene Gagnon in the Clint Eastwood-directed war film Flags of Our Fathers. Writing for the Honolulu Star-Advertiser, Burl Burlingame called it "the richest testament Hollywood has yet made about the paroxysm of World War II ... an astounding movie on every level". The following year, she played one of the principal characters—a woman desperate to get away from her abusive husband—on the short-lived television series Drive, which was cancelled by FOX midway through its first season run. In her review for the Los Angeles Times of the series' first two episodes, Mary McNamara described Lynskey as "especially compelling".
In 2008, Lynskey had a supporting role in the three-part Western miniseries Comanche Moon, which aired on CBS. The series received mixed reviews from critics, but People commented that Lynskey's performance was among the "best" in the cast. Later that year, she returned to New Zealand to star in the romantic drama Show of Hands, for which she earned a nomination for Best Actress at the Qantas Film and Television Awards.
Lynskey received strong reviews in 2009 for Away We Go, a comedy-drama directed by Sam Mendes in which she played a woman who has suffered a series of miscarriages. Wesley Morris of The Boston Globe called it "the best performance in the movie". Next, she co-starred as Matt Damon's wife, Ginger, in Steven Soderbergh's dark comedy The Informant!. The film—which is based on real events—was described as "devilish fun" by Rolling Stone, while Geoffrey Macnab said that Lynskey provided "sterling support" in his review for The Independent. Soderbergh told the Los Angeles Times, "She is so watchable. You never quite know what you're going to get, you just know it's going to be good. Her rhythms are really unusual, like her cadence and her reaction times to things, and the way she sort of lays out a sentence. It's just really, really interesting". While making the film, Soderbergh discouraged Lynskey from contacting the real person on which her character was based, as he wanted her to reach her own conclusion about whether Ginger had been involved in her husband's crimes. "I decided she had no idea what was going on", she later said. "She was trusting, she was the kind of wife who thinks her job is to stay in the house and take care of the kids ... even though some things didn't necessarily add up ... She wasn't asking too many questions". Lynskey counts her time working on The Informant! as one of her favorite experiences.
Matt Damon said something to me that I really have lived by ever since ... “At the end of your career, when someone looks over your filmography, all they remember is if the movie was good or not. They’re not saying, ‘Oh, he [played] that crazy character!’ [or] ‘Oh, all those people were in that movie’ ... all people know is if the movie was good or not” ... so, if you consistently choose good scripts ... you’re going t
Melanie Lynskey