[1] Santasiere, of French and Italian ancestry, was born and raised in New York City, the 12th of 13 children, and grew up in extreme poverty.

Following graduation, beginning in 1927, Santasiere taught mathematics at the Angelo Patri Middle School in the Bronx.

Santasiere was also an expert in the Reti Opening, the King's Gambit, and the Vienna Game.

[3] In 1923, Santasiere tied for 13th/14th place at Lake Hopatcong (9th American Chess Congress, Frank Marshall and Abraham Kupchik won).

In 1929, he took third place, behind Herman Steiner and Jacob Bernstein, at Buffalo (New York State Championship).

In September 1945, he played in a US vs USSR radio match on tenth board against David Bronstein, and lost both games.

[7] Santasiere tied for 9-13th places at the 1960 Canadian Open Chess Championship in Kitchener, with 6/10; Anthony Saidy won.

[8] On Saturday, May 11, 1968, at the Miami Beach Chess Club in Miami Beach, Florida, Santasiere, billed as "The American Chess Champion", competed in a marathon simultaneous exhibition versus 21 opponents.

He played piano, and was a keen chef who frequently hosted dinner parties.

As late as the Canadian Open Chess Championship, 1960 (which I won with many uneasy moments), he was able to run up to me and exclaim about a pretty but simple knight sacrifice he’d just played, "I’ve just won the most beautiful game of my life".

A true lover of chess – a type seldom found among top competitors today.

[10]Denker and Parr describe Santasiere's strong spiritual interests; he advocated what Henry Adams called "conservative Christian anarchy".

During his life, Santasiere wrote three novels, 13 books of essays, 14 collections of short stories, and 30 volumes of a personal journal.