The group recently released an album especially for children
Barenaked Ladies frontman Steven Page has left the Canadian group under "mutual agreement", according to the band's website.
The singer, who pleaded not guilty in July after being arrested in New York for possessing cocaine, will "pursue solo projects", the posting said.
Page said: "I love them and wish them all the best in the future."
Guitarist and singer Ed Robertson said: "It's the start of a new chapter for all of us. Here's to the future."
As well as Robertson, the remaining band members Jim Creeggan, Kevin Hearn and Tyler Stewart plan to continue recording and touring.
Page described his former band members as "my brothers".
He said: "We've grown up together over the past 20 years."
The group pulled out of performing at the Disney Music Block Party last year after Page's arrest.
Known for their clean image and cross-generational appeal, the group recently released an album for children called Snacktime.
They are best known for hits such as One Week and Pinch Me.