The play portrays the visit of an elderly professor and his glamorous, much younger second wife, Yelena, to the rural estate that supports their urban lifestyle.

Two friends—Vanya, brother of the professor's late first wife, who has long managed the estate, and Astrov, the local doctor—both fall under Yelena's spell while bemoaning the ennui of their provincial existence.

Matters are brought to a crisis when the professor announces his intention to sell the estate, Vanya and Sonya's home, with a view to investing the proceeds to achieve a higher income for himself and his wife.

[1] By elucidating the specific changes Chekhov made during the revision process—these include reducing the cast from almost two dozen down to nine, changing the climactic suicide of The Wood Demon into the famous failed homicide of Uncle Vanya, and altering the original happy ending into an ambiguous, less final resolution—critics such as Donald Rayfield, Richard Gilman, and Eric Bentley have sought to chart the development of Chekhov's dramaturgical method through the 1890s.

Rayfield cites recent scholarship suggesting Chekhov revised The Wood Demon during his trip to the island of Sakhalin, a prison colony in Eastern Russia, in 1891.

Astrov is forced to depart to attend to a patient, after making a speech on the preservation of the forests, a subject he is passionate about.

A storm starts and Astrov talks to Sonya about the house's suffocating atmosphere; he says Serebryakov is difficult, Vanya is a hypochondriac, and Yelena is charming but idle.

Serebryakov proposes to solve the family's financial problems by selling the estate and investing the proceeds, which will bring in a significantly higher income (and, he hopes, leave enough over to buy a villa for himself and Yelena in Finland).

Vanya begins to rage against the professor, blaming him for his own failures, wildly claiming that, without Serebryakov to hold him back, he could have been a second Schopenhauer or Dostoevsky.

Vanya complains of the heaviness of his heart, and Sonya, in response, speaks of living, working, and the rewards of the afterlife: "And our life will grow peaceful, tender, sweet as a caress….

The play was adapted as the stage-play Dear Uncle by the British playwright Alan Ayckbourn, who reset it in the 1930s Lake District.

Directed by Jack Serio and using a translation by Paul Schmidt, the cast featured Will Brill as Astrov, Julia Chan as Yelena, David Cromer as Vanya, Will Dagger as Telegin, Marin Ireland as Sonya, Bill Irwin as Serebryakov (replaced by Thomas Jay Ryan), Virginia Wing as Marina, Ann McDonough as Maria, and Nathan Malin as Yefim.

[11] Among the actors who have played Uncle Vanya on Broadway are Ralph Richardson, Nicol Williamson, Tom Courtenay, and Derek Jacobi.

Since April 2024, a Broadway production of Uncle Vanya has been staged in the Vivian Beaumont Theater by director Lila Neugebauer.

The cast includes Steve Carell as Uncle Vanya, Allison Pill as Sonya, William Jackson Harper as Astrov, Alfred Molina as Alexander Serabryakov, Anika Noni Rose as Yelena, Jonathan Hadary as Telegin/"Waffles," Jayne Houdyshell as Mama Voinitski, and Mia Katigbak as Marina.

[12][13] Other actors who have appeared in notable stage productions of Uncle Vanya include Michael Redgrave, Paul Scofield, Peter O'Toole, Albert Finney, Franchot Tone, Cate Blanchett, Peter Dinklage, Jacki Weaver, Antony Sher, Ian McKellen, Richard Armitage, Simon Russell Beale, William Hurt, George C. Scott, Donald Sinden, Michael Gambon, Trevor Eve, and Laurence Olivier.

The cast: Alexander Wladímirowitsch Serebrjaków; Linus Ebner; Jeléna (Elena) Andréjewna: Sarah Quarshie; Iwán Petrówitsch Wojnízkij, genannt „Onkel Wanja“: Ekkehard Freye; Sofja Alexándrowna (Sonja): Nika Mišković; Michaíl Lwówitsch Ástrow: Alexander Darkow; María Wassíljewna: Antje Prust; Iljá Iljítsch Telégin: Adi Hrustemović; Marína: Nina Karimy;