Helburn was a co-founder of the Theatre Guild in 1919. There she acted first as a literary manager, reviewing scripts, then as casting director, and later became co-producer with Lawrence Langner."Theresa Helburn Theater Collection", Bryn Mawr College, accessed August 30, 2017 The Guild brought original dramas from European and American playwrights, such as George Bernard Shaw and Eugene O'Neill, to the Broadway stage, and established relationships with such notable actors as Alfred Lunt and Lynn Fontanne, whom Helburn cast together for the first time in 1924. She married scholar John Baker Opdycke in 1922. In 1925, just six years after the establishment of the production company, Helburn presided over the groundbreaking ceremony for the new Guild Theatre (now August Wilson Theatre)."Gov. Smith Lays Stone for Guild; Recalls Theatrical Conditions of His Boyhood at New Theatre in West 52d Street". The New York Times. December 3, 1924. Retrieved February 28, 2022. She also supported new plays and playwrights in smaller theatres.
