Lithgow and Molina will play Ben and Jorge, respectively, partners of 38 years who marry at City Hall. After Jorge loses his job, the two are forced to live apart.
"We'll be playing the main roles in the best script I've read in years," said Lithgow in a statement, "a vivid portrait of marriage, with all its joy, folly and occasional heartbreak."
Lithgow was last seen on Broadway in a Tony-nominated performance in The Columnist. The Tony and Emmy winner's stage credits also include All My Sons, Dirty Rotten Scoundrels, The Sweet Smell of Success, The Front Page and Beyond Therapy. His film work includes "The World According to Garp," "Terms of Endearment" and "Shrek," and his TV credits include "Third Rock From the Sun," "Dexter" and "How I Met Your Mother."
Molina is a three-time Tony nominee (Red, Fiddler on the Roof, Art), whose film credits include "Chocolat," "An Education" and "Spider-Man 2." His TV work includes "Ladies Man," "Bram and Alice" and "Monday Mornings."
Sachs is also a producer of "Love Is Strange," alongside Lars Knudsen and Jay Van Hoy, and Lucas Joaquin. Filming is slated to begin in August in New York City.