Pena's music from the first half of his career touched on Delta blues, jazz, morna, flamenco, folk, and rock and roll.

Pena is probably best known for writing the song "Jet Airliner," a major 1977 hit for the Steve Miller Band and a staple of classic rock radio; and for appearing in the 1999 documentary film Genghis Blues, wherein he displayed his abilities in the field of Tuvan throat singing.

[1][2] In February 1969, Pena's band played for a week at the Electric Factory in Philadelphia, Pennsylvania, opening twice for both Frank Zappa and the Mothers of Invention and the Grateful Dead.

He also played in the T-Bone Walker Blues Band during the early 1970s, including an appearance in the Montreux Jazz Festival in 1972.

After moving to San Francisco in 1971, Pena called the Grateful Dead office, which helped find him work.

Pena temporarily suspended his musical career to care for his wife Babe, who was experiencing kidney failure.

The Derek Trucks Band also covered Pena's song "Something to Make You Happy" on their 2009 Grammy Award-winning album Already Free.

At the same time he heard an interview with the English musician Jill Purce, one of the pioneers of overtone chanting in the West, on KPFA radio in Berkeley, California, and obtained her recording.

Pena said: After playing the CD continuously for several months and driving many of my friends away by making weird noises while experimenting with my voice, I finally learned a few of the basic techniques of this fascinating group of vocal styles by remembering the styles of some of the blues greats of the past – especially Charlie Patton, Tommy McClennan, and Chester "Howlin' Wolf" Burnett.

He used a device called an Optacon to scan the pages and convert the printed words into tactile sensations he could read with his finger.

Pena attended a performance of Tuvan throat singing at the Asian Art Museum of San Francisco on February 6, 1993.