In 2006, Yotsuba to! received an Excellence Award in manga category at Japan Media Arts Festival where the jury citation praised the vivid characters and gentle atmosphere the manga has. In 2008, the series was nominated for the 12th Osamu Tezuka Culture Award and the Eisner Award "Best Publication for Kids" category, but did not win either one. It was also a runner-up for the first annual Manga Taishou award. In 2016, the series, along with Hanagami Sharaku, was awarded the 20th Tezuka Osamu Cultural Prize Grand Prize.

The series was first published in English by ADV Manga as Yotsuba&!. Six volumes were released from June 6, 2005 to October 31, 2007 before publication was discontinued. Yen Press has published the series since September 15, 2009. It has also been published in Spanish by Norma Editorial since November 2005. It has been licensed in Polish by Wydawnictwo Kotori.