- 1607 - Some Apalachees ask for friars; the first visit the following year
- 1612 - Spaniards reject Apalachees' request for a permanent mission.
- 1625 - Apalachees begin to send food supplies overland to St. Augustine.
- 1633 - Two friars establish first permanent missions in Apalachee.
- 1638 - First Spanish soldiers arrive in Apalachee.
- 1640's - Missions in Apalachee expand dramatically; brisk trade with Havana begins.
- 1645 - First deputy governor assigned to Apalachee.
- 1647 - First mention of San Luis mission by name (although it is likely one of the first missions established in 1633); uprising by some Apalachees.
- 1651 - Soldiers and deputy governor withdrawn at friars' request.
- 1654 - English ship at St. Marks used as pretext to return soldiers to Apalachee.
- 1656 - San Luis moves to its present site; Apalachees help quell Timucua revolt.
- 1657 - Governor Rebolledo conducts visitation of Apalachee's 10 missions and 25 satellite villages; garrison expands.
- 1674 - Presence of non-Apalachee tribes revealed at San Luis.
- 1675 - Permanent settlement of Spanish families had begun; garrison expanded; Bishop Calderón makes a formal visit; the name "San Luis de Talimali" first appears and "Jinayca" disappears; San Luis revealed to be the most populous mission with 1400 Apalachees.
- 1676 - Fray Juan de Paiva composes ballgame manuscript at San Luis.
- 1681 - Beginning of deteriorating relations with Apalachicola neighbors as Governor Juan Marques Cabrera tries to impose a mission on them.
- 1685 - Governor Marques Cabrera's imposition of a brutal deputy governor, Antonio Matheos, strains relations with Apalachees.
- 1687 - Relations improve when Governor Marques Cabrera deserts his post and Antonio Matheos is removed.
- 1688 - Governor Diego de Quiroga y Losada plans an elaborate new blockhouse at San Luis, but attention is turned to the Chattahoochee River instead.
- 1689 - Apalachee carpenters build a fort near Columbus, Georgia to thwart English traders on the Chattahoochee River.
- 1691 - Spanish and Apalachee forces destroy the new Chattahoochee fort and withdraw to San Luis.
- 1695 - Work begins on the new blockhouse at San Luis which was almost completed by the early spring of 1696.
- 1698 - San Luis Apalachees seriously alienated when Spaniards commandeer some of their houses and land; Spaniards also take lumber intended for church repairs and force Indians to build houses for them.