Schlamme moved from his native Houston to New York in 1973. After serving in several low level positions for production companies, he founded his own company, Schlamme Productions, in 1980. From there, he produced campaigns for a number of musicals, including Cats. He directed the first "I Want My MTV!" advertising campaign in 1981 for producer Buzz Potamkin, and singer/songwriter Amy Grant's 1985 music video "Find a Way" for producers Fred Seibert and Alan Goodman. Throughout the 1980s, he produced a number of specials on various entertainers including Whoopi Goldberg and Rowan Atkinson.
"You almost never see how anyone travels from point A to point C [in most TV shows]. I wanted the audience to witness every journey these people took. It all had a purpose, even seeing them order lunch. It just seemed to be the proper visual rhythm with which to marry Aaron's words. I got lucky that it worked."
Schlamme's nearly decade-long collaboration in television with writer-producer Aaron Sorkin began in early 1998 when they found they shared common creative ground on the soon to be produced Sports Night. Their successful partnership in television is one in which Sorkin focuses on writing the scripts while Schlamme executive produces and occasionally directs; they have worked together on Sports Night, The West Wing, and Studio 60 on the Sunset Strip. Schlamme will create the look of the shows, work with the other directors, discuss the scripts with Sorkin as soon as they are turned in, make design and casting decisions, and attend the budget meetings; Sorkin tends to stick strictly to writing.
Schlamme first worked with Aaron Sorkin on his short-lived ABC comedy/drama Sports Night, for which he directed 16 of its 45 episodes. Their biggest break was in 1999, teaming up again on their hit political drama The West Wing. He directed the pilot episode and from then on served as the executive producer until 2003. He directed 14 episodes of The West Wing in addition to serving as executive producer. In 2003, at the end of the fourth season, Schlamme and Sorkin left the show due to internal conflicts at Warner Bros. TV not involving the NBC network, thrusting producer John Wells into an expanded role as showrunner.
In early October 2005 a pilot script dubbed Studio 7 on the Sunset Strip for a new TV series, written by Sorkin and with Schlamme attached as producer, started circulating around Hollywood and generating interest on the web. A week later, NBC bought from Warner Bros. TV the right to show the TV series on their network for a near-record license fee in a bidding war with CBS. The show's name was later changed to Studio 60 on the Sunset Strip.
In September 2006, the pilot for Studio 60 aired on NBC, directed by Schlamme. The pilot was critically acclaimed and had high ratings,[according to whom?] but Studio 60 experienced a significant drop in audience by mid-season. The show was cancelled after one season.
Schlamme's direction is characterized by use of a technique called the "walk and talk": sequences consisting of single lengthy tracking shots involving multiple characters engaging in conversation as they move through the set. Characters enter and exit the conversation as the shot continues without any cuts.