2021–present: Solo activities
On June 24, 2021, Jo released "Story of Us" for JTBC's television series Monthly Magazine Home.
On September 23, Jo released "Autumn Memories" (가을 상자), a collaboration song with Lee Seok-hoon. On September 24, WakeOne announced that Jo will be releasing her first single album titled Glassy on October 7, with lead single of the same name. Following her debut as a soloist, Jo was nominated for Rookie of the Year at the 36th Golden Disc Awards, Best New Female Artist at the 2021 Mnet Asian Music Awards, and Rookie of the Year at the 31st Seoul Music Awards.
On April 11, 2022, Jo was cast in her first acting role, the Playlist Studio web series Mimicus. On May 17, it was announced that Jo would be releasing her first extended play titled Op.22 Y-Waltz: in Major on June 2, with lead single "Love Shhh!". The album debuted at number five on South Korea's Circle Album Chart. On June 7, she achieved her first ever music show win on SBS M's The Show for "Love Shhh!" On August 11, Jo released the promotional single "Maybe" through Universe. On September 13, Jo released the song "Can You Feel My Heart" as part of the soundtrack for the KBS2 television series The Law Cafe.
On October 8, it was announced that Jo would be releasing her second single album titled Op.22 Y-Waltz: in Minor on October 24. Later that same month, Jo released the song "Run (Female Ver.)" for the Netflix television series The Fabulous. In December 2022, Jo made a special appearance in episode 7 of the second season of Work Later, Drink Now portraying Sieun, a juvenile delinquent. Jo's performance was well received by critics such as Choi Hye-jin writing for MT Star News, who praised Jo's natural acting and described the performance as "short, but leaving a strong impression". In addition to her appearance, Jo also released the track "Drink It, Girls!" as part of the soundtrack for Work Later, Drink Now 2.
On June 29, 2023, it was announced that Jo had been cast in the second season of the Netflix television series Squid Game, which was released in December 2024. She also appeared in season 3 of the series, which was released in June 2025. She played the role of Kim Jun-hee, also known as Player 222, where she gained significant attention for her acting in the series. On July 2, Jo released the track "Down (Juicy Juicy)" for tvN television series See You in My 19th Life. Three days later, she released a cover of Taeyeon's "A Poem Titled You". On July 25, it was announced that Jo would be releasing her second extended play titled Love All, alongside the lead single "Taxi", on August 9. On August 29, she and Zerobaseone's Sung Han-bin released the duet "Luv Luv Luv" as part of the soundtrack for the tvN series My Lovely Liar.
On October 25, 2024, Jo released the track "Spring Days pass" for tvN television series Jeongnyeon: The Star Is Born. On June 25, 2025, it was announced that Jo would release her third extended play Episode 25 on July 14, two years after her previous release. On July 7, the pre-release track "Growls and Purrs" was released, followed by the release of Episode 25 on July 14. On July 13, Jo Yu-ri revealed on the MBC variety show Omniscient Interfering View that she had officially renewed her contract with WakeOne.
On July 21, 2025, it was announced that Jo would be starring in the Netflix television series Variety, portraying the lead role of Seung-hee, an obsessive K-pop fan. On April 25, 2026, it was announced that Jo would be starring in the television series Love Virus, portraying the lead role of Im Mi-a, a criminal hunter.