Lou Reed might've been the jaded heart of the Velvet Underground, but John Cale started out as the brain. The Welsh musician co-founded the band with Reed, and brought in his avant-garde flourishes to make songs and albums that are still being emulated to this day. Then, he left.
Cale was part of the Velvet Underground from 1964 to 1968. He played on the band's first two albums and took an especially large role in the creation of the second album, White Light / White Heat. It's not a coincidence that the album is seen by many as the boldest and most experimental in the entire VU catalog.
John Cale left Velvet Underground in 1968

Despite being friends with Reed, Cale's desire to push the band in a more avant-garde direction did not gel with his bandmate. Reed wanted to be the main creative engine, and expressed as much to drummer Mo Tucker and guitarist Sterling Morrison. He told Tucker and Morrison he would quit the band unless they agreed to fire Cale before their third album. They did, reluctantly.
Cale went on to release a string of acclaimed solo albums and produce for Velvet Underground alum like Nico. The Velvet Underground took on a Reed-centric sound for the rest of the 60s, though they were done by 1970 (at least, in terms of the classic lineup). Cale and Reed did not speak again until 1987, when they both attended the funeral of artist and Velvet Underground promotor Andy Warhol.
To the surprise of nearly everyone, Cale and Reed made up, and agreed to reunite the classic Velvet Underground lineup. They recorded a live album and performed a series of tour dates in 1993, but it didn't take long for the old tensions to resurface, and Cale and Reed to fall out. They played together once more, during their Rock & Roll Hall of Fame induction in 1996.
Cale looks back fondly on the band

Cale spoke on his time with the Velvet Underground during a 2024 interview with Big Issue. Despite the numerous splits and disagreements with Reed, who died in 2013, the musician claimed that he looks back on his time with the band fondly.
"It felt like the centre of the artistic universe for a while," Cale explained. "The sense of humor was rapacious but there was also generosity and goodwill. When I look back at those days, we had run into this hidden source of talent. It was the strangest collection of people but also the most inspiring." Cale continues to release solo music, and collaborate with younger artists who have pulled heavily from his time with the Velvet Underground. It may have been brief, but it was impactful.