In 1980, Olmos was cast in the post-apocalyptic science fiction film Virus (復活の日 Fukkatsu no Hi), directed by Kinji Fukasaku and based on a novel written by Sakyo Komatsu.
 His role required him to play a piano while singing a Spanish ballad during the later part of the film.
Although not a box office success, Virus was notable for being the most expensive Japanese film ever made at the time.

From 1984 to 1989, he starred in his biggest role up to that date as the taciturn police Lieutenant Martin Castillo in the television series Miami Vice, opposite Don Johnson and Philip Michael Thomas, for which he was awarded a Golden Globe and an Emmy in 1985.
At this time, Olmos also starred in a short training video for the United States Postal Service entitled Was it Worth It?,
a video about theft in the workplace.
He was contacted about playing the captain of the USS Enterprise (NCC-1701-D) on Star Trek: The Next Generation when it was in pre-production in 1986, but declined.

Returning to film, Olmos became the first American-born Hispanic to receive an Academy Award nomination for Best Actor, in Stand and Deliver, for his portrayal of real-life math teacher, Jaime Escalante.
He directed and starred in American Me in 1992, and also starred in My Family/Mi Familia, a multi-generational story of a Chicano family.
He had a slight appearance in the video of the American rock band Toto, "I Will Remember" (1995), where he can be seen with actor Miguel Ferrer.
In 1997, he starred alongside Jennifer Lopez in the film Selena.
Olmos played Dominican Republic dictator Rafael Leónidas Trujillo in the 2001 movie In the Time of the Butterflies.
He also had a recurring role as U.S. Supreme Court Justice Roberto Mendoza in the NBC drama The West Wing.
From 2002 to 2004, he starred as a recently widowed father of a Hispanic L.A.-family in the PBS drama American Family: Journey of Dreams.

From 2003 to 2009, he starred as Commander William Adama in the Sci-Fi Channel's reimagined Battlestar Galactica miniseries, and in the television series that followed.
He directed four episodes of the show, "Tigh Me Up, Tigh Me Down" (1.9), "Taking a Break from All Your Worries" (3.13), "Escape Velocity" (4.4), and "Islanded in a Stream of Stars" (4.18).
He also directed a television movie based upon the show, The Plan.
Regarding his work on the show, he told CraveOnline, "I'm very grateful for the work that I've been able to do in my life, but I can honestly tell you, this is the best usage of television I've ever been a part of to date."

In 2006, he co-produced, directed, and played the bit part of Julian Nava in the HBO movie about the 1968 Chicano Blowouts, Walkout.
He also appeared in Snoop Dogg's music video "Vato".
In the series finale of the ABC sitcom George Lopez, titled "George Decides to Sta-Local Where It's Familia"; he guest-starred as the plant's new multi-millionaire owner.
More recently, he has been a spokesperson for Farmers Insurance Group, starring in their Spanish language commercials.

Olmos joined the cast of the television series Dexter for its sixth season, as a "brilliant, charismatic professor of religious studies".

Olmos starred in the second season of Marvel's Agents of S.H.I.E.L.D. as Robert Gonzales, the leader of a rival faction of S.H.I.E.L.D., for five episodes.
In 1980, Olmos was cast in the post-apocalyptic science fiction film Virus (復活の日 Fukkatsu no Hi), directed by Kinji Fukasaku and based on a novel written by Sakyo Komatsu.  His role required him to play a piano while singing a Spanish ballad during the later part of the film. Although not a box office success, Virus was notable for being the most expensive Japanese film ever made at the time.
From 1984 to 1989, he starred in his biggest role up to that date as the taciturn police Lieutenant Martin Castillo in the television series Miami Vice, opposite Don Johnson and Philip Michael Thomas, for which he was awarded a Golden Globe and an Emmy in 1985. At this time, Olmos also starred in a short training video for the United States Postal Service entitled Was it Worth It?, a video about theft in the workplace. He was contacted about playing the captain of the USS Enterprise (NCC-1701-D) on Star Trek: The Next Generation when it was in pre-production in 1986, but declined.
Returning to film, Olmos became the first American-born Hispanic to receive an Academy Award nomination for Best Actor, in Stand and Deliver, for his portrayal of real-life math teacher, Jaime Escalante. He directed and starred in American Me in 1992, and also starred in My Family/Mi Familia, a multi-generational story of a Chicano family. He had a slight appearance in the video of the American rock band Toto, "I Will Remember" (1995), where he can be seen with actor Miguel Ferrer. In 1997, he starred alongside Jennifer Lopez in the film Selena. Olmos played Dominican Republic dictator Rafael Leónidas Trujillo in the 2001 movie In the Time of the Butterflies. He also had a recurring role as U.S. Supreme Court Justice Roberto Mendoza in the NBC drama The West Wing. From 2002 to 2004, he starred as a recently widowed father of a Hispanic L.A.-family in the PBS drama American Family: Journey of Dreams.
From 2003 to 2009, he starred as Commander William Adama in the Sci-Fi Channel's reimagined Battlestar Galactica miniseries, and in the television series that followed. He directed four episodes of the show, "Tigh Me Up, Tigh Me Down" (1.9), "Taking a Break from All Your Worries" (3.13), "Escape Velocity" (4.4), and "Islanded in a Stream of Stars" (4.18). He also directed a television movie based upon the show, The Plan. Regarding his work on the show, he told CraveOnline, "I'm very grateful for the work that I've been able to do in my life, but I can honestly tell you, this is the best usage of television I've ever been a part of to date."
In 2006, he co-produced, directed, and played the bit part of Julian Nava in the HBO movie about the 1968 Chicano Blowouts, Walkout. He also appeared in Snoop Dogg's music video "Vato". In the series finale of the ABC sitcom George Lopez, titled "George Decides to Sta-Local Where It's Familia"; he guest-starred as the plant's new multi-millionaire owner. More recently, he has been a spokesperson for Farmers Insurance Group, starring in their Spanish language commercials.
Olmos joined the cast of the television series Dexter for its sixth season, as a "brilliant, charismatic professor of religious studies".
Olmos starred in the second season of Marvel's Agents of S.H.I.E.L.D. as Robert Gonzales, the leader of a rival faction of S.H.I.E.L.D., for five episodes.
Edward James Olmos