On the day of the founding, Lasuen's heart was made glad by the presentation of fifteen children for baptism. At the end of 1800 there were 362 neophytes, 372 horses and cattle, and 1582 smaller animals. The crop of 1800 was 1900 bushels.
Padre Antonio de la Concepción Horra, who was shortly after deported as insane, and who gave Presidente Lasuen considerable trouble by preferring serious charges against the Missions, was one of the first ministers.
In February of 1801 the two padres were attacked with violent pains in the stomach and they feared the neophytes had poisoned them, but they soon recovered. Padre Pujol, who came from Monterey to aid them, did not fare so well for he was taken sick in a similar manner and died. Three Indians were arrested, but it was never decided whether poison had been used or not. The Indians escaped when being taken north to the presidio, and eventually the padres pleaded for their release, asking however that they be flogged in the presence of their families for having boasted that they had poisoned the padres.
In August, 1806, a disastrous fire occurred, destroying all the manufacturing part of the establishment as well as a large quantity of wool, hides, cloth, and 6000 bushels of wheat. The roof of the church was also partially burned. At the end of the decade San Miguel had a population of 973, and in the number of its sheep it was excelled only by San Juan Capistrano.
In 1818 a new church was reported as ready for roofing, and this was possibly built to replace the one partially destroyed by fire in 1806. In 1814 the Mission registered its largest population in 1076 neophytes, and in live-stock it showed satisfactory increase at the end of the decade, though in agriculture it had not been so successful.
Ten years later it had to report a great diminution in its flocks and herds and its neophytes. The soil and pasture were also found to be poor, though vines flourished and timber was plentiful. Robinson, who visited San Miguel at this time, reports it as a poor establishment and tells a large story about the heat suffocating the fleas. Padre Martin died in 1824.
In 1834 there were but 599 neophytes on the register. In 1836 Ignacio Coronel took charge in order to carry out the order of secularization, and when the inventory was made it showed the existence of property, excluding everything pertaining to the church, of $82,000. In 1839 this amount was reduced to $75,000. This large valuation was owing to the fact that there were several ranches and buildings and two large vineyards belonging to the Mission. These latter were Santa Isabel and Aguage, with 5500 vines, valued at $22,162.
The general statistics from the founding in 1797 to 1834 give 2588 baptisms, 2038 deaths; largest population was 1076 in 1814. The largest number of cattle was 10,558 in 1822, horses 1560 in 1822, mules 140 in 1817, sheep 14,000 in 1820.
In 1836 Padre Moreno reported that when Coronel came all the available property was distributed among the Indians, except the grain, and of that they carried off more than half. In 1838 the poor padre complained bitterly of his poverty and the disappearance of the Mission property. There is no doubt but that here as elsewhere the Mission was plundered on every hand, and the officers appointed to guard its interests were among the plunderers.
In 1844 Presidente Duran reported that San Miguel had neither lands nor cattle, and that its neophytes were demoralized and scattered for want of a minister. Pico's 1845 decree warned the Indians that they must return within a month and occupy their lands, or they would be disposed of; and in 1846 Pico reported the Mission sold, though no consideration is named, to P. Rios and Wm. Reed. The purchasers took possession, but the courts later declared their title invalid. In 1848 Reed and his whole family were atrociously murdered. The murderers were pursued; one was fatally wounded, one jumped into the sea and was drowned, and the other three were caught and executed.