Watson was born in Columbia County, Georgia. After graduating from Mercer University, he became a school teacher. Watson later studied law and was admitted to the Georgia bar in 1875. He joined the Democratic Party and in 1882 was elected to the Georgia Legislature.
As a state legislator, Watson struggled unsuccessfully to curb the abuses of the powerful railroad corporations. A bill subjecting railroads to county property taxes was voted down after US Senator Brown offered to provide the legislators with round-trip train fares to the Louisville Exposition. Watson resigned his seat and returned to the practice of law before his term expired.
Watson began to support the Farmers' Alliance platform, and was elected to the US Congress as an Alliance Democrat in 1890. In Congress, he was the only Southern Alliance Democrat to abandon the Democratic caucus, instead attending the first Populist Party congressional caucus. At that meeting, he was nominated for Speaker of the House by the eight Western Populist congressmen. Watson was instrumental in the founding of the Georgia Populist Party in early 1892. The Populist Party advocated the public ownership of the railroads, steamship lines and telephone and telegraph systems. It also supported the free and unlimited coinage of silver, the abolition of national banks, a system of graduated income tax and the direct election of United States Senators.
That year, Watson was elected to the Senate and served until March 1893. After being defeated he returned to work as a lawyer in Thompson, Georgia. He also served as editor of the People's Party Paper.
In the 1896 presidential election the leaders of the Populist Party entered into talks with William Jennings Bryan, the proposed Democratic Party candidate. They thought they had an agreement that Watson would become Bryan's running mate. After giving their support to Bryan he announced that Arthur Sewall, a conservative politician with a record of hostility towards trade unions, would be his vice presidential choice. This created a split in the Populist Party, some refused to support Bryan whereas others, such as Mary Lease, reluctantly campaigned for him. Watson's name remained on the ballot and won 217,000 votes.
The defeat of Bryan severely damaged the Populist Party. While Populists continued to hold power in a few Western states, the party ceased to be a factor in national politics.
As his own personal wealth grew, Watson denounced socialism, which had drawn many converts from the ashes of populism. He became a vigorous anti-semitic and anti-Catholic crusader who called for the reorganization of the Ku Klux Klan. He was the party's presidential candidate in 1904 but won only 117,183 votes. The party's fortunes continued to decline and in the 1908 presidential campaign, attracted only 29,100 votes.
Watson, through his publications Watson's Magazine and The Jeffersonian he continued to hsbr great influence on public opinion. In 1913 he played a prominent role in inflaming public opinion in the case of Leo Frank, Jewish-American factory manager who was accused of of the murder of Mary Phagan, 13 year-old factory worker. Watson and the Southern press sensationalized the case, directing racist and anti-Semetic comments against Frank while making wild, unsubstantiated charges. Frank was convicted and sentenced to death by hanging, but after a lengthy appeals process, his sentence was commuted to life in prison by the governor of Georgia. Watson railed against the decision and called for Georgians to take justice into their own hands. On August 17, 1915, Frank was dragged from his prison cell by a group of men and lynched.
Watson rejoined the Democratic Party and in 1920 was elected to the Senate. However, he died in 1922 of a cerebral hemorrhage at age 66.