 The member of a politically active family, Isaac's six brothers included John T. Struble of Iowa, and George R. Struble, former speaker of the Iowa House of Representatives.He was the granduncle of Bob Struble, Sr. and great-granduncle of Bob Struble, Jr.

Isaac Struble of Le Mars, Iowa, was born near Fredericksburg, Virginia.His great-grandfather, Dietrich Struble of Albig bei Alzey, Germany, had sailed to Philadelphia in 1748, settling outside German Valley, New Jersey (since renamed Long Valley).