The play debuted
off Broadway April 14, 2001, at the
Joseph Papp Theater in
New York City.
 It was directed by Loretta Greco, produced by
George C. Wolfe, and the executive producer was Fran Reiter. Rosemarie Tichler was the artistic producer.
The play is a montage of reminiscences, memories, testimonials and
roman a clefs of "Miss Rachel," or Nanny, as the young Ruben Santiago, Jr. calls her. Largely abandoned by his parents, Ruben finds that Nanny becomes his surrogate family. Various incidents in Ruben's and Nanny's life are portrayed, with a large cast of quirky minor characters—friends, boarders, family members, visitors, relatives, and so on—providing commentary on Nanny's strength of character, intelligence, and morality.
The play included several songs, either sung by the characters in the play or as ambient music heard via a radio or through a window.
Bill Sims Jr. provided the original music, as well as performing on-stage acoustic guitar for the play.
Lackawanna Blues is intended to be a one-man show. The actor narrating the play (an adult Ruben) was intended to portray more than 20 other characters, as well as the starring role of the young Ruben.
The play was very well received.
The New York Times called it a "tour de force."
 Playwright Ruben Santiago-Hudson won an
OBIE special citation for Lackawanna Blues, while Bill Sims, Jr. won an OBIE for his music.