Harry Pillsbury beat Emanuel Lasker at St Petersburg in 1895. Lasker had become recognized as world champion by defeating William Steinitz in a match in 1894. (Steinitz changed his name from Wilhelm to William when he became a US Citizen in 1888.) I can't find any Americans who beat Steinitz while he was champion (1866-1894).
Question about First American

Emmanuel Lasker wrote that it was the Paris tournament of May-June 1900 that “first opened the eyes of the chess world to the caliber of skill that Marshall possessed.” There he tied for third (with Maróczy), behind Lasker and Pillsbury. He defeated Lasker, the world champion, to inflict Lasker’s only loss in the tournament and his only loss to Marshall for four decades.
So Frank Marshall belongs on the list.

thats a diificult question because in the early years of chess (as it is today) the world chmapion was not definite and wins and losses were not often properly recorded

I see a D. Martinez beating Steinitz in Philadelphia in 1882, in a match game. Probably the same D. Martinez who was president of the Franklin Chess Club.

Americans who have defeated reigning world champions (with thanks to Spektrowski's post):
Pillsbury beat Lasker 1895
Marshall beat Lasker 1900
Dake beat Alekhine 1932
Fine beat Alekhine 1938
Reshevsky beat Botvinnik 1955
Fischer beat Spassky 1972
Seirawan beat Karpov 1982
Gulko beat Kasparov 1990
Kamsky beat Kasparov 1992
Nakamura beat Anand 2011
Nakamura beat Carlsen 2016
Just came across a question in the endless quiz asking: Who was the last American to defeat a reigning world champion? The answer given was Yasser Seirawan (who beat Kasparov in 1986, he also beat Karpov in 1982 at age 22).
Here is another question. Who was the first American to defeat a reigning world champion? In 1932 Arthur Dake (then age 22, born in Portland, Oregon, died in 2000) defeated Alekhine in 38 moves (Alekhine was world champion from 1927 - 1935 and again from 1937 until his death in 1946). Can anyone come up with an answer to this question that is earlier? (Morphy played before there was a recognized world champion.)