Meighan was born to John and Mary Meighan in Pittsburgh, Pennsylvania. His father was the president of Pittsburgh Facing Mills and his family was well off.
Meighan's parents encouraged him to go to college but he refused. At the age of 15 his father sent him to work shoveling coal which quickly changed his mind. He attended St. Mary's College studying pharmacology. After 3 years of study Meighan decided he wished to pursue acting.
After dropping out of college in 1896 Meighan became a juvenile player in the Pittsburgh Stock Company headed by Henrietta Crosman. He was paid $35 a week.
Meighan soon found success. He first appeared on Broadway in 1900. In 1904 Meighan appeared in "The Two Orphans". His breakthrough role came in 1908 when he appeared with William Collier Sr. in "The Dictator". That was followed by a leading role in "The College Widow", which had a successful run on Broadway for the 1907–1908 season. It was during this run he met his wife Frances Ring.
Despite his film career Meighan remained devoted to the theatre during his life.
In 1914 he abandoned theatre for the new movie industry; which was still in its infancy at the time. His first film was shot in London, titled "Dandy Donovan, the Gentleman Cracksman". This film led to a contract with Famous Players-Lasky. His first US film was in 1915, "The Fighting Hope". During the next 2 years Meighan's career would take off. In 1918 he made a propaganda film for World War I titled, "Norma Talmadge and Thomas Meighan in a Liberty Loan Appeal". He then played opposite Mary Pickford in M'Liss.
In 1919 Meighan hit stardom. One of his best known films at the time was the 1919 The Miracle Man which featured Lon Chaney Sr.. This film is now believed to be lost except for brief clips. This was followed with Cecil B. DeMille's Male and Female which starred him opposite Gloria Swanson and Lila Lee. Most of the cast returned for the 1920 film, Why Change Your Wife? which also co-starred Bebe Daniels. In April 1925, Meighan and Swanson produced a short film, directed by Allan Dwan for the annual "Spring Gambol" for The Lambs. This film, sometimes known as Gloria Swanson Dialogue made in Lee DeForest's sound-on-film Phonofilm process, was made as a joke for the live event, showing Swanson trying to crash the all-male club.
His popularity continued through the Roaring Twenties with him starring in several pictures. In 1924 he played in The Alaskan opposite Estelle Taylor and Anna May Wong. In 1927, Meighan starred in The City Gone Wild opposite Louise Brooks.
His final silents, both produced by Howard Hughes in 1928, were The Mating Call, which was critical of the KKK, and The Racket, which was nominated for an Academy Award for Best Picture. Both were thought lost until rediscovered in private collections in 2006 and restored by University of Nevada, Las Vegas and shown on Turner Classic Movies.
His first talkie feature film was The Argyle Case (1928). Meighan was nearing 50 and feared his popularity might wane, and decided to go into real estate. It took until 1931 for him to return to the screen with Young Sinners. He would go on to make only four additional talkies until his illness sidelined him from acting. His last film was Peck's Bad Boy in 1934.
Meighan commanded a salary of $5,000 a week for much of his career. At one point it reached $10,000 a week.
Meighan met Frances Ring (July 4, 1882 – January 15, 1951). Ring was an attractive stage actress, on Broadway when Meighan was also appearing. She was a sister of popular singer Blanche Ring. Actor and director A. Edward Sutherland was a nephew of both Blanche Ring and Meighan. Sutherland's mother, Julie, was a sister of Blanche and Frances Ring.
Meighan and Ring became inseparable and soon married. They remained married until his death in 1936. Their happy marriage was considered a strong one prompting one writer to remark, "Thomas Meighan and Rin Tin Tin were the only Hollywood stars who had never seen a divorce court". The couple had no children.
Meighan was involved in some of the more scandalous moments of silent film history; albeit as a helping hand. On October 25, 1916 in New Jersey he was the sole witness to Jack Pickford and Olive Thomas's secretive wedding.
In March 1923, Douglas Gerrad, in need of help bailing his friend Rudolph Valentino out of jail for bigamy, called up a fellow Irishman named Dan O'Brien who happened to be with Meighan at the time. Meighan barely knew Valentino but put up a large chunk of the bail money, and with the help of June Mathis and George Melford, Valentino was eventually freed.
In the mid-1920s, Meighan became obsessed with Florida after talks with his realtor brother James E. Meighan. He bought property in Ocala, Florida in 1925. In 1927, he built a home in New Port Richey, Florida where he would spend his winters. He intended to shoot his film We're All Gamblers there, however, filming was moved to Miami.
The Meighans hoped to draw other celebrities to the area. On July 1, 1926, The Meighan Theatre opened with a screening of Meighan's movie The New Klondike. Meighan himself was not present but sent a congratulatory telegram.
In 1930 sound was added to the theatre. Meighan himself appeared this time, pushing the button to start the sound. The theatre closed in 1934, a victim of the Depression. It reopened in 1938 under the name The New Port Richey Theatre. The theatre is still open as a community playhouse under the name Richey Suncoast Theatre.
In 1934, Meighan was diagnosed with cancer. In 1935, he underwent surgery at Doctors Hospital in Manhattan. He finally succumbed to cancer at 9:10pm on July 8, 1936, passing away at his home in Great Neck, New York. Many of his family were present.
Meighan was originally buried at Calvary Cemetery in Queens. After resting there for almost a year, his remains were moved to a family plot at Saint Mary Cemetery in Meighan's hometown of Pittsburgh.
Meighan was a large donater to various Catholic charities and the Federation for the Support of Jewish Philanthropic Societies. Many of his later films survive and have been released on DVD.