Otto was born in 1435 as the eldest son of
Otto I, Count Palatine of Mosbach-Neumarkt. He succeeded his father in 1461 and spent most of his life in
Neumarkt. He managed to end the controversy of
Wolfstein, a castle and city opposite Neumarkt with the same rights which was ruled by the
House of Wolfstein, after acquiring the pawned castle from the
Neuschönenbergs. Otto II also had a strong interest in astronomy and mathematics, which led to his title "Mathematicus", and he established an observatory on the castle at Neumarkt. In 1490 he retired all active rulership over Mosbach-Neumarkt to
Philip,
Elector of the Palatinate, and spent the remainder of his life in scientific pursuits. Otto died in Neumarkt in 1499 childless and was buried in the Church of St Maria. Mosbach-Neumarkt passed to the Electoral Palatinate after his death.