Other films he has appeared in are Hostiles, Heat, Mystery Men, Avatar, A Million Ways to Die in the West, and the television series Penny Dreadful.

[7] In 2024, Studi appeared on the television series Finding Your Roots and learned that Eugene Philpott, who was listed on his birth certificate, was not his biological father.

[6][12] A year later, he was cast with Eric Schweig for TNT's film The Broken Chain, about the historic Iroquois League that was based in the area of central and western present-day New York state.

This was part of a group of productions shown over 14 months on TNT as its "Native American initiative", including three television movies and several documentaries.

In 2002, Studi brought to life the character of Police Lieutenant Joe Leaphorn, for a series of PBS movies based on Tony Hillerman's novels set in the Southwest among the Navajo and Hopi.

In 2005, Studi portrayed a character based on chief Opechancanough, leader of the Powhatan Confederacy in Virginia, in the film The New World directed by Terrence Malick.

In 2009, Studi appeared as Major Ridge, a leader of the Cherokee before the Native American removal to Indian Territory, in Trail of Tears.

[15] At the 90th Academy Awards, Studi introduced a tribute to military movies,[16] and gave part of his speech in the Cherokee language, of which he is a fluent speaker.

"[20] In December 2020, The New York Times ranked him #19 in its list of the "25 Greatest Actors of the 21st Century (So Far)," noting "Wes Studi has one of the screen’s most arresting faces — jutting and creased and anchored with the kind of penetrating eyes that insist you match their gaze.

Lesser directors like to use his face as a blunt symbol of the Native American experience, as a mask of nobility, of suffering, of pain that’s unknowable only because no one has asked the man wearing it.

Studi serves as honorary chair of the national endowment campaign of the Indigenous Language Institute in Santa Fe.