She is best known for her roles as Janey Briggs in the comedy film Not Another Teen Movie (2001), Lexie Grey in the ABC medical drama series Grey's Anatomy (2007–2012; 2021), Alex Danvers in the DC Comics superhero series Supergirl (2015–2021), and Katherine "Kat" Landry in the Hallmark drama The Way Home (2023–present).

She soon began acting by appearing in local television commercials and a syndicated teen news show, Hall Pass.

[7] At age 16, Leigh met her future husband, twenty year old Nathan West, when they both attended auditions for the pilot of an unsuccessful WB series titled Saving Graces.

[5] This led to abuse of drugs, which quickly escalated into addiction; she was told by the director of Not Another Teen Movie that she looked unhealthily thin.

[5] Around that time, she and West also attended a Christian church service, at the invitation of a friend, which helped them in recovery, and the two were subsequently married.

She started hosting in local TV shows and modeling; in 2001, Leigh nabbed the lead role in the box-office success Not Another Teen Movie as Janey Briggs opposite Chris Evans.

[clarification needed][14][15][16][17] On June 18, 2017, a single "Spirit of Samba" by Laurent Voulzy was released featuring Leigh, Nina Miranda, Luisa Maita and Eloisia; in France it reached the 99th position on the Syndicat National de l'Édition Phonographique (SNEP) chart.

[18][19] From 2015 to 2021, Leigh starred in the CBS/CW DC Comics television series Supergirl as Alex Danvers, the elder adoptive sister of the titular character and a scientist and government agent at the DEO.

[24] The couple worked together in 2000 on the television series 7th Heaven, playing Mary Camden's (Jessica Biel) troubled friends Frankie and Johnnie.

[24][27] She also supports The Thirst Project, a non-profit organization in America which aims to bring safe drinking water to communities around the world.