Of all of France’s early modern colonial ventures, the least studied and most obscure are the French efforts to establish settlements, missions, and plantations in Guiana. Still, the seventeenth-century French colonies in Guiana had much in common with the sixteenth-century French efforts to colonize Florida and Brazil, and their trajectories were every bit as dramatic and their outcomes equally dismal. Although not sponsored as Huguenot refuges in the New World from Catholic oppression in the Old, and thus not burdened with the fierce competition between Protestant and Catholic colonists that plagued the sixteenth-century ventures, the Guiana colonies were also prey to deep internal divisions over piety and morality, and even more over power and the purpose of the colony. Were they primarily missions to the Native peoples, plantations, or commercial ventures focused on locating sources of precious metals or establishing plantations? This paper examines the role of clerics in the genesis, financing, trajectories, and collapse of the earliest French colonies in Guiana, in particular two colonies founded about ten years apart, in 1643 and 1652. I will the argue that whereas historians have often assumed that missionaries and evangelizing were often little more than an encumbrance to early colonial ventures, useful mostly for raising funds in France, in reality clerics played a central role in shaping chartered colonial companies and the colonies they founded, for good and for ill.