[3] San Gregorio enjoys mild weather throughout the year, except for some remarkably chilly mornings, even in the summer.

Although snow is very rare in the coastal lowlands, 4.0 inches (10 cm) fell in San Gregorio on January 21, 1962.

Temperatures exceed 90 °F (32 °C) on an average of only 1.8 days, but have occurred in April, May, June, July, August, September, and October.

Freezing temperatures 32 °F (0 °C) or below are more common, occurring on an average of 13.1 days, and have been recorded in January, February, March, April, May, June, October, November, and December.

Once this was Ohlone country, where the Portola Expedition found the native people to be most gracious, offering food and guidance.

[5] The first European land exploration of Alta California, the Spanish Portolà expedition, passed through the area on its way north, camping for three days near today's San Gregorio, October 24–26, 1769.

Franciscan missionary Juan Crespi noted in his diary on Tuesday October 24, "…we came to a small valley where there is a good-sized village of very fine, very well-behaved, fair and beaded heathens who received us with a great deal of hospitality and pleasure.

Here in the valley there is a great deal of soil, and a stream in midst with a good-sized flow of delicious water, on its way to empty into the sea at where they have the village.

A good spot for a good-sized mission; I named it Nuestro padre Santo Domingo, Our Father Saint Dominic."

[14] San Gregorio has been the site of several film locations and television show episode scenes.