His parents were the stars of the television sitcom I Love Lucy, and Ball's pregnancy was part of the story line, which was considered daring in 1952.

As a testament to how interested the American public was in Lucy's TV baby, Arnaz appeared on the cover of the first issue of TV Guide with the headline "Lucy's $50,000,000 baby", ($570,000,000 in 2023 dollars)[2] because revenue from advertising tie-ins was expected to top that amount.

In 1968, he had a guest-starring role as Jerry and Suzie's drum-playing friend Tommy in the episode, "The Hombre Who Came to Dinner: Part 2", from the show The Mothers-in-Law, executive-produced and directed by his father.

In 1974, Arnaz played the title role in the Western movie Billy Two Hats with Gregory Peck.

In 1977, he was the lead in the film Joyride opposite fellow children of famous actors Melanie Griffith, Robert Carradine, and Anne Lockhart.

Arnaz's acting extended into the late 1980s with various appearances on television, and a leading role in the short-lived TV series Automan, which ran from 1983 to 1984 in only 12 episodes.

[7] From about 2002 to 2007, he was vice-president of the board of Directors of the Lucille Ball–Desi Arnaz Center in Jamestown, New York.

[10] On October 15, 2011, Arnaz performed in Babalu at the Coolidge Auditorium of the Library of Congress.

After they broke up, writer and music producer Michael Tell offered to marry Duke as a way out of the scandal.

Their marriage lasted 13 days, and Duke later told her son, Sean Astin, that Arnaz was his biological father.

Arnaz and Astin developed a close relationship, although genetic tests later revealed that Tell was his biological father.

Arnaz's granddaughter Desiree S. Anzalone (daughter of Julia), a photographer, died from breast cancer on September 27, 2020, at age 31, six years after it was first diagnosed.