Busfield studied drama at East Tennessee State University and traveled frequently with the Actors Theater of Louisville, which took him to Europe and Israel.

The following year, Busfield relocated to Los Angeles to join the cast of Reggie (ABC, 1983), a short-lived comedy based on the British television series The Fall and Rise of Reginald Perrin (BBC, 1976–79).

The part was his first mature role to date, and the producers requested that Busfield, who was then clean shaven, grow a beard to help sell his image as a married man and father.

Over the course of the show's four-season run, Elliot came to personify the best and worst aspects of the series: a successful advertising executive and father, Elliot also infuriated his friends and family (and viewers) with his marital infidelity and competitive streak with partner Michael Steadman (Ken Olin), all of which went on while his wife Nancy (Patricia Wettig) struggled with ovarian cancer.

[6] Busfield appeared as the nominal villain in the popular Kevin Costner fantasy Field of Dreams in 1989, and in 1990, replacing Tom Hulce as the lead in A Few Good Men, a Broadway production written by Aaron Sorkin, with whom he would later enjoy fruitful collaborations.

During this period, Busfield also began his recurring role as Pulitzer Prize–winning White House correspondent—and love interest to Allison Janney's C.J.

[3] Busfield kept a foot on both sides of the camera from 2000 on; directing and executive producing the successful CBS drama Without a Trace (2002–09) and appearing occasionally as the wheelchair-using divorce attorney for Anthony LaPaglia's Jack Malone.

On the latter, he also co-starred on the short-lived Aaron Sorkin series as Cal Shanley, the occasionally nerve-plagued control director for the program's self-titled show-within-a-show.

[7] In 2020, Busfield appeared as a guest on the Studio 60 on the Sunset Strip marathon fundraiser episode of The George Lucas Talk Show.

Busfield remains a stage actor and director whose Broadway credits include A Few Good Men and Brighton Beach Memoirs, where he was star Matthew Broderick's understudy.

With elder brother Buck Busfield, he is co-founder of the B Street Theatre in Sacramento, California,[9] where he has appeared in and directed numerous contemporary works.