Lee Patrick’s debut on the Broadway theatre stage began in November 1922 as part of the supporting ensemble cast for Adele and Fred Astaire in the Jerome Kern and Anne Caldwell musical The Bunch and Judy that ran for eight weeks. It was not until September 1924 that Patrick was once again on the Broadway stage, in an 8-week run of The Green Beetle at the Klaw Theatre. The John Willard drama set in San Francisco’s Chinatown featured her as the lead characters’ daughter who escaped a murder attempt. Although playwright William H. McMaster’s The Undercurrent closed the same month it opened in 1925 after 23 performances, that was only the first of 5 plays in which Patrick honed her talent that year. The Backslapper (1925) was a political drama that ran for 33 performances with Patrick in a supporting role as Mrs. Kennedy. A trend was developing as Patrick began to flex her comedic muscles for the remainder of 1925: Bachelors’ Brides was a farce in which she played a guardian angel; It All Depends was another comedy, The farce A Kiss in a Taxi that ran for 103 performances and featured another up and coming talent Claudette Colbert, rounded up Patrick’s stage work of 1925.

The Shelf comedy in 1926 was brief at 32 performances, but otherwise notable for being the debut stage performance of Thelma Ritter who, like Lee Patrick, would go on to become a comedy sidekick in films. Patrick only acted in three plays in 1927: the very brief 12-performance comedy Baby Mine which brought her together with Humphrey Bogart for the first time; the equally brief The Matrimonial Bed; and Nightstick, an 84-performance run through January 1928 that also featured Thomas Mitchell who would go on to win an Academy Award for his performance in Gone with the Wind. The 24-performance run of The Common Sin was the only other play she did in 1928. The Ring Lardner and George S. Kaufman June Moon gave Patrick her longest run of her stage career, 273 performances in 1929 and 1930, and an additional 48 performances in 1933. She rounded out 1930 with the 13-performance run of Room of Dreams. Privilege Car was her first play of 1931, but she soon was on stage with George M. Cohan in the musical Friendship and finished out that year with 17 performances as Meg in Little Women One of the briefest plays of her career was The Girl Outside in 1932, which only ran for 8 performances; however, that one came on the heels of the very successful Blessed Event that had run for 115 performances. After the very brief run of Shooting Star in 1933, and the equally brief Slightly Delirious, her only play of 1934, Patrick began to look towards a film career. Knock on Wood and Abide With Me did not fare much better for her. She had a long run of 169 performances in Stage Door in 1936–1937, but only did one more Broadway play after that, the unsuccessful comedy Michael Drops In.

Lee Patrick had the starring role in her first film, Strange Cargo, an early American sound production for Pathé released on March 31, 1929. In this remake of producer Benjamin Glazer’s Missing Man, British actor George Barraud played her leading man. It was another six years before she made another film, The Casino Murder Case for MGM. While she only had a bit part as a nurse in the film, it brought her together for the first time with Leo G. Carroll, with whom two decades later she would work on the television series Topper. She remained in Hollywood and appeared in Border Cafe (1937). Over the next several years she played numerous supporting roles, without attracting much critical attention. Patrick appeared in The Maltese Falcon (1941) as Effie Perine, the loyal and quick-thinking secretary of Humphrey Bogart’s Sam Spade. Perine was one of Patrick’s most enduring film characterizations. That same year, she appeared in a leading role as an intelligent, crime-solving nurse in The Nurse’s Secret. Among her other films are The Sisters (1938), Now, Voyager (1942), Mrs. Parkington (1944), Gambler’s Choice (1944), Mildred Pierce (1945), Wake Up and Dream (1946), Caged (1950), There’s No Business Like Show Business (1954), Vertigo (1958), Auntie Mame (1958), Pillow Talk (1959), Summer and Smoke (1961), and 7 Faces of Dr. Lao (1964).[33] Her final film role was a reprise of her Effie Perine character in a reworking of the Sam Spade story The Black Bird. Starring George Segal as Sam Spade, Jr., forced to continue his father’s work and to keep his increasingly sarcastic secretary, the film attempted to turn its revered predecessor into a comedy.

Lee Patrick appeared on television in the CBS situation comedy Topper (1953–1955) with Leo G. Carroll, Anne Jeffreys, and Robert Sterling. She made several appearances as the mother of Ida Lupino in the CBS sitcom Mr. Adams and Eve (1957–1958), also starring Howard Duff. In 1963, she appeared as Aunt Wilma Howard in the episode “Skeleton in the Closet” of Walter Brennan’s CBS sitcom The Real McCoys. In 1965, she appeared as Mrs. Ashton Durham in the episode “It’s a Dog’s World” of Hazel and as Cora Prichard in an episode entitled “Noblesse Oblige” during the show’s final season. She also turned in a hilarious voice performance as “Mrs. Frumpington” in an episode of the CBS animated series The Alvin Show, which may also be heard on the soundtrack LP by David Seville and The Chipmunks. Ms. Patrick also made three appearances in the TV series “I Married Joan.”