After graduation, she returned to Austin to study film directing at the University of Texas. Her M.F.A. thesis feature was a lo-fi/sci-fi road movie, The Slow Business of Going (2001), shot on the fly in hotel rooms in nine cities around the world. The 2002 NY Critics Poll listed it as one of the year’s “best first films” and it now resides in MoMA’s permanent film collection.
While a student and later a film lecturer at UT-Austin, she co-founded and directed the Cinematexas International Short Film Festival (1997-2007) as a showcase of pioneering experimental cinema and sonic art.
She was invited to serve as the projections designer and video director for the 2004 Athens Summer Olympics for its extraordinary opening and closing ceremonies, and has been working as a projections designer ever since, in parallel with her work in cinema. In 2009, she created a unique series of in-situ large-scale HD projections for the inauguration of the new Acropolis Museum in Athens.
Her second feature Attenberg (2010) premiered in main competition at the Venice Film Festival, where it won the Coppa Volpi Award for Best Actress (Ariane Labed). It went on to win more than a dozen best film awards at festivals worldwide, was Greece’s official submission to the 2012 Academy Awards®, and was runner-up for the Lux prize for Best European Film.
For over ten years she has operated Haos Film, a pioneering filmmaker-run production & postproduction studio based in Athens. Among her credits as a producer are three films directed by Yorgos Lanthimos — Kinetta (2005), Dogtooth (2009, Un Certain Regard prize winner at Cannes), and Alps (2011, Osella Award winner at Venice) along with a variety of debut films by rising young directors. She was also a co-producer on Richard Linklater's Before Midnight (2013), filmed in Messinia, Greece — wherein she also appeared as an actress.
The Capsule (2012), a "mediterranean gothic fantasy" written in collaboration with Polish artist Aleksandra Waliszewska, was commissioned by the Deste Foundation for Contemporary Art as both a film and an installation. It premiered at dOCUMENTA(13) in Kassel, followed by competition slots at the Locarno, Toronto and Sundance film festivals.
She was one of 70 directors invited by the Venice Film Festival to participate in the commemorative project "Venezia 70 - Future Reloaded", for which she made a short science fiction film, 24 Frames Per Century (2013). Also in 2013, she directed two episodes of the historical drama TV series Borgia, executive produced by Tom Fontana and Barry Levinson.
She has served as a jury member at the Berlin and Locarno film festivals, and as jury president at the Gothenburg and London film festivals. She was a creative advisor at the 2012 and 2014 Sundance Feature Film Program Directing Lab in Utah. In June 2016, together with celebrated producer Christos Konstantakopoulos, they were the co-instigators and hosts of the inaugural Sundance Mediterranean Screenwriter Workshop in Greece to promote and support emerging talent from the region.
Her third feature Chevalier (2015) — a buddy comedy set on a yacht in the Aegean Sea —had international premieres at the Locarno, Toronto, and New York film festivals to critical acclaim, and won the Best Film prize in official competition at the BFI-London Film Festival. It's been so far included in several international "Best of 2016" film critics' lists.
In 2014, she was invited to Harvard University’s Visual and Enviromental Studies department as a visiting lecturer in film production, and received the Film Study Center’s Robert Gardner Fellowship. In 2015, she was awarded Harvard's Radcliffe Institute Fellowship in cinema.
Tsangari was honored by the Lincoln Center Film Society as its 2015 Filmmaker in Residence (a creative initiative sponsored by Jaeger-Le Coultre) during which she developed her screenplay for her upcoming English-language film White Knuckles, a female-driven screwball-noir-comedy.