Grade was raised Orthodox-leaning, and he studied in yeshiva as a teenager, but ended up with a secular outlook, in part due to his poetic ambitions.

He studied for several years with Reb Avrohom Yeshaya Karelitz, the Chazon Ish (1878–1953), one of observant Judaism's great Torah scholars.

In 1932, Grade began publishing stories and poems in Yiddish, and in the early 1930s was among the founding members of the "Young Vilna" experimental group of artists and writers.

Grade's second wife, Inna (née Hecker), translated a number of his books into English; she died in New York City on May 2, 2010.

Grade's short story, "My Quarrel with Hersh Rasseyner," describes the chance meeting of a Holocaust survivor with an old friend from the mussar Yeshiva.

[8] While less famous than Isaac Bashevis Singer or Sholem Aleichem, Chaim Grade is considered among the foremost stylists in Yiddish.

His papers were very numerous and consumed much space of the apartment he shared with his wife Inna in the Amalgamated Housing Cooperative in the Northwest Bronx.