Macha Makeïeff was born in Marseille to a Protestant family of Russian and Italian descent. She studied at the Conservatoire d'Art Dramatique de Marseille, where she met the pianist Pierre Barbizet. She studied literature and art history at the Sorbonne and at the Art Institute of Paris. At the same time, she worked as a reader for Flammarion and contributed to the magazine Cinématographe. Her meeting with Antoine Vitez was decisive, as he entrusted her with her first production at the Théâtre des Quartiers d'Ivry.

Macha Makeïeff is the author and director, with Jérôme Deschamps, of more than twenty shows created within the framework of their company ("Deschamps et Makeïeff") which they founded and direct together. Most of their shows are performed in France and abroad during long tours. 

Macha Makeïeff was artistic director of the Théâtre de Nîmes from 2003 to 2008. She created the visual identity of the Theatre and produced all the programs and posters.

In opera, she directed with Jérôme Deschamps Offenbach's Les Brigands (Amsterdam Opera and Opéra Bastille in Paris, musical director Louis Langrée) and Mozart's L'Enlèvement au sérail (Aix en Provence, musical director Marc Minkowski; Opéra de Lausanne, musical director Christophe Rousset). In 2004, she directed Moscow-Cheryomushki at the Lyon Opera with Alexander Lazarev, for which she designed the sets and costumes. Since then, she has created several remarkable shows such as Mozart Short Cuts (Grand Théâtre du Luxembourg and Cité de la Musique, musical director Laurence Equilbey), La Veuve Joyeuse (Opéra de Lyon, musical director Gérard Korsten), L'Étoile by Chabrier and Zampa by Hérold (Opéra Comique, musical director William Christie), La Calisto by Cavalli at the Théâtre des Champs-Elysées (musical director : Christophe Rousset), Le Bœuf sur le toit by Darius Milhaud and Les Mamelles de Tirésias by Francis Poulenc at the Opéra de Lyon and the Opéra Comique (musical director: Ludovic Morlot), productions for which she is responsible for the staging, sets and costumes.

Macha Makeïeff founded "Les Films de mon Oncle" with Jérôme Deschamps and Sophie Tatischeff in 2000. She is in charge of the artistic direction of the DVDs and publications and is responsible for the editorial line.

Macha Makeïeff is also a visual artist and has set up her studio at "7bis", a unique creative space in Paris: she has created costumes, sets, props, and visual and sentimental identities for numerous shows and events.

In 2010, she founded her own theater company: Mademoiselle.

Macha Makeïeff succeeded Jean Louis Benoît as director of the Théâtre de la Criée - Centre Dramatique National - on July 1st 2011. She created Les Apaches and Ali Baba in 2013; Les Âmes offensées : Les derniers chasseurs Inuits and Les Soussous de Guinée in 2014 and Les Guerriers Massai in 2017 with the notebooks of ethnologist Philippe Geslin. As well as Lumières d'Odessa (2014), Trissotin ou les Femmes Savantes (2015), La Fuite! by Mikhail Boulgakov in 2017. Lewis versus Alice is created at the Avignon Festival on July 14, 2019. Finally, Tartuffe Théorème created in November 2021.

Macha Makeïeff left the direction of La Criée in July 2022, when her mandate ended. She continues her activities as a director, set designer and costume designer through Mademoiselle, her theater and visual arts company, which she sees as a unifying artistic label for talent.