[6] From 1881 until his death, George represented Mississippi in the United States Senate, where he was recognized for his skills in debate, helped frame the future Sherman Anti-Trust Act, introduced the bill for agricultural college experiment stations, and encouraged the establishment of the Department of Agriculture.

Alarmed by the proposed Lodge Bill, which would have provided for federal supervision of elections, he campaigned in Mississippi for a constitutional convention in order to legally disenfranchise African-Americans, without resorting to violence, fraud, and other extralegal measures that had been used prior.

[7] He was a major figure during the Mississippi Constitutional Convention of 1890 itself, leading a hardline faction promoting the disenfranchisement of blacks without disenfranchising whites (as opposed to those who wanted to apply property and educational requirements to whites and blacks), and successfully defended the constitution before the Senate and the Supreme Court.

He is buried, along with his wife, Elizabeth Brooks (Young) George,[9] in Evergreen Cemetery in North Carrollton, Mississippi.

Z. George High School in North Carrollton, Mississippi is named in his honor, which is less than 2 miles (3.2 km) from his burial place.