His father was murdered when he was six, and he succeeded under the regency of his uncle, Frederico Landi, 4th Prince of Val di Taro.

This ended Spanish rule and put Monaco under French protection, recognizing and guaranteeing Monegasque sovereignty.

As a consequence Honoré lost his Spanish and Italian possessions, but was compensated by King Louis XIII of France with the marquisate Les Baux and the title of Duke of Valentinois.

During his reign he did much to extend, rebuild and transform the Genoese fortress that was the Grimaldi's stronghold into what is today Monaco's Princely Palace.

A collector's silver coin has been issued by the Treasury of Monaco portraying Honoré II on the occasion of the 400th anniversary (1612 – 2012) of the use of the title "Sovereign Prince."