Nėris was born in Kiršai, in the current district of Vilkaviškis. She graduated from the University of Lithuania where she studied Lithuanian and German language and literature. After that she was a teacher in Lazdijai, Kaunas, and Panevėžys. Her first collection of poems, titled Anksti rytą (In the Early Morning), was published in 1927.

In 1928, Nėris graduated from the University and was appointed to teach German language at the Seinų žiburys' Gymnasium in Lazdijai. Until 1931, Nėris contributed to nationalist and Roman Catholic publications. While studying German in Vienna, in 1929, Nėris met Lithuanian medical student Bronius Zubrickas and became attracted to him. Zubrickas had socialist views and Nėris engaged in socialist activities in order to court him.

In 1931, Nėris moved to live in Kaunas, where she gave lessons and edited Lithuanian folk tales. In the second collection of Nėris's poetry, The Footprints in the Sand, there is evidence of the onset of a profound spiritual crisis. In the same year, verses containing revolutionary motifs were published in the pro-communist literary journal Trečias frontas (The Third Front).

A promise to work for communism was also published. However, it was not written by her but by the chief ideological editor of Trečias frontas, Kostas Korsakas, and communist activist Valys Drazdauskas (Nėris was more interested in writing poetry than in declarations, politics and theories about art).

Salomėja Nėris was awarded the State Literature Prize in 1938.

Controversy surrounds her involvement with the Soviet occupation. She was appointed as a deputy to the Soviet - backed "People's Seimas" and was a member of the delegation to the Supreme Soviet of the Soviet Union to request Lithuania be accepted into the Soviet Union. Nėris was requested to write a poem in honour of Stalin and was subsequently awarded the Stalin Prize (posthumously, in 1947). After that, she wrote more verses on the theme, as encouraged by the USSR Communist Party officials. She spent World War II in the Russian SFSR.

Salomėja Nėris returned to Kaunas but fell ill and died of liver cancer in a Moscow hospital in 1945. Her last poems show deep affection for Lithuania itself. She was buried in Kaunas, in a square of the Museum of Culture, and later re-interred in the Cemetery of Petrašiūnai.

Her original pen name was Neris, the name of the second biggest Lithuanian river. In 1940, she received a letter from her students calling her a traitor to her homeland and asking her not to use the name of the River Neris. She added a diacritic on "e" and used only the pen name Nėris, which until then had no particular meaning.