His paternal grandparents were Duke Albert II of Brunswick-Grubenhagen and his wife Countess Elisabeth of Waldeck.
Together with his father and brothers, he took part in a military campaign in southern Germany in 1546, during the Schmalkaldic War, which ended unsuccessfully at Ingolstadt.
From this marriage only one daughter reached adulthood: Because Ernest had no sons, after his death, his duchy was inherited by his younger brother Wolfgang.
When he, too, died without a male heir, the duchy was inherited by their youngest brother, Philip II.
With Philip's death, the Brunswick-Grubenhagen line of the House of Guelph died out, and the duchy was merged back into Brunswick-Wolfenbüttel.