Knox entered the Sophomore class of Hamilton College, Clinton, New York, in 1827, and a year later entered the corresponding class at Yale College, the former institution having been temporarily broken up by dissensions.

In the winter of 1841, he was married to Prudence H. Blish, of Wethersfield, Illinois, whose death in 1846 so depressed him that he undertook a variety of additional employments as a relief.

He became the proprietor and occasional editor of the village newspaper, engaged extensively in farming, and established a very thriving business in the manufacture of agricultural implements.

Owing to failing eyesight, he went to Europe in October 1859, and after a successful operation for cataract returned in January 1861.

From his ample estate he gave during his lifetime the sum of $10,000 to Yale, $20,000 to Hamilton College, and upwards of $30,000 to educational institutions in his adopted county, including St. Mary's School.