2016–2021
To commemorate her fifth year as a solo artist, Lisa released her Letters To U EP as a limited edition LP on March 23, 2016. She released a mini-album titled Lucky Hi Five! on April 20, 2016. She released the single "Brave Freak Out", which was used as the first opening theme to the 2016 anime television series Qualidea Code, and the single also includes the song "AxxxiS", which was used as the second opening theme to Qualidea Code, on August 24, 2016. She released the single "Catch the Moment" on February 15, 2017; the title track was used as the theme song to the 2017 anime film Sword Art Online The Movie: Ordinal Scale. Lisa moved to the Sacra Music record label under Sony Music Entertainment Japan in April 2017. She released her fourth studio album Little Devil Parade on May 24, 2017. She held a two-day concert at the Saitama Super Arena on June 24 and 25, 2017. She released her single "Datte Atashi no Hero." (だってアタシのヒーロー。; lit. "Because He is My Hero") on August 2, 2017; the song was used as the second ending theme for the second season of the anime series My Hero Academia. Her single "Ash", which was released digitally on October 1, 2017, was used as the second opening theme to the anime television series Fate/Apocrypha; the single received a physical release on November 29, 2017.
Lisa performed "Thrill, Risk, Heartless" as the theme song for the video game Sword Art Online: Fatal Bullet. The song was released digitally on January 9, 2018. She released two compilation albums titled Lisa Best -Day- and Lisa Best -Way- on May 9, 2018. She released a double A-sided single titled "Akai Wana (Who Loves It?) (赤い罠 (who loves it?)) / Adamas" on December 12, 2018. The song "Adamas" was used as the first opening theme to the 2018 anime series Sword Art Online: Alicization; it was released digitally on October 7, 2018. She is featured on Hiroyuki Sawano's song "Narrative", which was used as the ending theme song of the anime film Mobile Suit Gundam Narrative under the name "SawanoHiroyuki[nZk]:Lisa". Her single "Gurenge" (紅蓮華, Red Lotus), used as the first opening theme song for the 2019 anime series Demon Slayer: Kimetsu no Yaiba, was released digitally on April 22, 2019 and received a physical release on July 3, 2019. She collaborated with FictionJunction in performing the song "From the Edge" which is used as the first ending theme to Demon Slayer: Kimetsu no Yaiba. The song was released digitally on September 1, 2019. Her single "Unlasting" was released on December 11, 2019, with the title track being released digitally on October 21, 2019; "Unlasting" was used as the third ending theme to Sword Art Online: Alicization. She appeared at the 2019 Kōhaku Uta Gassen. She released her digital single "Aijō" (愛錠, Love Lock) on August 17, 2020; the song is used as the theme song for Japanese drama series 13. On October 14, 2020, she released her fifth studio album Leo-Nine, and also a single titled "Homura" (炎, Flame); The song was used as the theme song for the anime film Demon Slayer: Kimetsu no Yaiba – The Movie: Mugen Train. "Homura" won the Grand Prix at the 62nd Japan Record Awards.
In July 2020, Lisa's "Gurenge" single surpassed 1 million downloads since its release. The single is the first by a female artist to surpass 1 million downloads in the history of Oricon's digital single ranking chart. It is the third overall single in the chart's history to do so, after Kenshi Yonezu's 2018 single "Lemon", and his 2019 single "Uma to Shika". In October 2020, "Homura" peaked at No. 8 on the Billboard Global 200.
On August 4, 2021, Lisa announced that she would be going on hiatus following reports from Shūkan Bunshun alleging that her husband Tatsuhisa Suzuki had been engaged in an extramarital affair. She later gradually resumed her music activities, beginning with a Hokkaido concert on August 28. She released the single "Hadashi no Step" on September 8, 2021; the title song is used as the theme song to the television drama Promise Cinderella.