Lea was the great-grandson of an earlier Luke Lea who was a two-term Congressman from Tennessee in the 1830s. Initially an ardent supporter of Democrat Andrew Jackson, the elder Lea later became a member of the Whig Party. Lea's maternal great-grandfather was William Cocke, who served in the U.S. Senate from 1796 to 1797, and again from 1799 to 1805.
The younger Lea attended public schools and then the University of the South in Sewanee, Tennessee, graduating with a bachelor's degree in 1899, and receiving his master's degree in 1900. Lea was the manager of the famed "Iron Men" of the 1899 Sewanee Tigers football team, who won five road games in six days, and outscored opponents 322 to 10. Lea is credited with putting together that season's team schedule. He then attended the Columbia Law School in New York City, from which he graduated in 1903. He was admitted to the bar the same year, and began to practice in Nashville.
In addition to practicing law, Lea formed a company to purchase the Nashville American newspaper. Reorganized as the Nashville Tennessean, Lea served as its first editor and publisher. He later merged the Tennessean with the Nashville Democrat, and his newspaper was a leading proponent of prohibition.
One of Lea's associates at the American and later the Tennessean was Edward W. Carmack, and Lea became involved in Democratic Party politics as a member of the faction led by Carmack. In 1908, Carmack was shot and killed by Duncan Brown Cooper, a former editor of the American, and Cooper's son Robin; Carmack wounded Robin Cooper with shots of his own. The Coopers were part of the Democratic Party faction led by Malcolm R. Patterson, who was elected governor in 1906, and whom Lea had challenged unsuccessfully for the Democratic nomination in 1908. Duncan and Robin Cooper were both convicted of second-degree murder and sentenced to prison. Duncan Cooper's conviction was affirmed on appeal, after which he received a pardon from Patterson. Robin Cooper won an appeal and the right to a retrial, but no prosecutor was willing to re-try the case, and Robin Cooper went free. Lea then assumed leadership of the Carmack faction, which succeeded at causing Patterson to withdraw from the 1910 campaign.
He was elected to the Senate by the Tennessee General Assembly in 1911; after 10 unsuccessful ballots, Lea's name was introduced as a compromise choice, and he was selected on the 11th ballot. He was an enthusiastic supporter of most of the progressive policies of Democratic President Woodrow Wilson, a fellow native of the South and only the second Democrat elected President (in 1912) since the end of the Civil War. During the 63rd Congress, Lea was chairman of the Senate Committee on the Library (of Congress).
Socially progressive but fiscally conservative, Lea actively supported lowering tariffs, the creation of the Federal Reserve System, the regulation of major corporations and the breaking up of trusts. He also supported women's suffrage and a national prohibition amendment. He allied with Robert La Follette and supported his seaman's act. He approved of the eight-hour day and opposed child labor.
In 1913, Lea began his most ambitious undertaking in the Senate when he attempted to launch a federal investigation of the railroads and political corruption in Tennessee. The investigation encouraged the railroads to cease distributing free passes as political favors, but the growing crisis of the First World War eventually overshadowed concerns about corruption and the investigation was shelved.
During Lea's term, the Seventeenth Amendment changed the method of election of Senators from election by the state legislatures to direct popular vote. Lea supported this measure. Lea contended for the 1916 Democratic nomination for the seat but was defeated by Kenneth McKellar, a colleague of Memphis political "boss" E. H. Crump. McKellar went on to serve six terms, and is Tennessee's longest-serving senator. Despite his lame duck status, Lea continued to work on the progressive agenda. He voted to confirm Louis Brandeis to the Supreme Court, and supported a number of progressive measures in the Senate including immigration reform, the Shipping Act of 1916, and the Revenue Act of 1916.
Shortly after the end of Lea's Senate term, the U.S. entered World War I. Lea volunteered and was commissioned as an artillery officer, serving in Europe, where he was promoted to the rank of colonel. In January 1919, Lea and a group of officers from his unit, the 114th Field Artillery, traveled to Kasteel Amerongen in the Netherlands in a failed attempt to seize the recently exiled German Kaiser Wilhelm II and bring him to the Paris Peace Conference for potential trial for war crimes. One of the officers accompanying Lea was Larry MacPhail, later the part-owner and general manager of the Cincinnati Reds, Brooklyn Dodgers and New York Yankees and father of baseball executive Lee MacPhail. Lea was a recipient of the Distinguished Service Medal for his World War I service.
After the close of the war, Lea returned to Nashville and resumed operation of his newspaper. In 1919 he was one of the founders of the American Legion and served prominently in various leadership roles. In 1929 Governor Henry H. Horton nominated Lea for appointment to the Senate seat vacated by the death of Lawrence D. Tyson. Lea declined, choosing instead to remain active in the banking and real estate businesses. Horton then nominated William Emerson Brock, who accepted. In the 1920s, Lea was a major investor in the Nashville investment banking firm of Caldwell & Company, due in part to his friendship with its founder Rogers Caldwell. Accusations of corruption were subsequently made about the bank, and Lea and his associates became the subject of rumor and innuendo. The book At Heaven's Gate by poet and novelist Robert Penn Warren is said to be a roman à clef about the events of this era in the Nashville area, as are aspects of the novel A Summons to Memphis by the novelist Peter Matthew Hillsman Taylor.
Lea was indicted in North Carolina with others, including his eldest son, for bank fraud resulting from the 1930 collapse of the Central Bank and Trust Company of Asheville, North Carolina, a bank with which he had become affiliated through his connection with Caldwell & Company. Both Lea and his son were tried in North Carolina in 1931. L. E. Gwinn, a prominent Memphis attorney whose specialty was criminal law, was brought in along with other attorneys, and the detailed preparation of the North Carolina case was entrusted to him. The Leas were convicted on three of seven counts. After the Leas’ appeals were exhausted and after the U.S. Supreme Court denied their petition for the writ of certiorari, both Leas reported for imprisonment at Raleigh in May 1934. Lea received a parole in April 1936, and he received a full pardon in June 1937. To the end of his life, Lea maintained that he and his son were wrongly prosecuted and convicted and that the prosecution was political in nature, with Lea being made the scapegoat for the Central Bank and Trust’s failure by his Republican foes in North Carolina and Tennessee.
Lea made many efforts to reintegrate himself into Tennessee business and political life after his release, but his interests in his newspapers and other investments had been liquidated or placed into receivership during his imprisonment. He died in Nashville in 1945 at the age of 66 and is buried in that city's Mount Olivet Cemetery.
Lea Heights in Nashville's Percy Warner Park, a place offering an excellent view of the downtown Nashville skyline, is named in his honor. The original land grant establishing Percy Warner Park was donated by Lea and his family to Nashville, and the park is named for Lea's father-in-law.
In 1906, Lea married Mary Louise Warner. They were the parents of Luke Lea Jr. and Percy Warner Lea. Mary Lea died while Luke Lea was en route to France during World War I.
Lea married Percie Warner in 1920; she was the sister of his first wife. Luke and Percie Lea were the parents of Mary Louise, Laura, and Overton.