In 2010, at the age of 17, Henningsen was cast in her first professional production as Penny Pingleton in Hairspray at the Woodminster Amphitheater in Oakland, California.
In November 2014, she made her New York Philharmonic debut as Kim Ravenal in a staged concert production of Kern and Hammerstein’s Show Boat. A live taping of the production later aired on PBS on October 16, 2015.
Later that year, Henningsen starred as Beth in the musical Diner, based on Barry Levinson’s 1982 film of the same name with music and lyrics by Sheryl Crow. The musical, directed and choreographed by Kathleen Marshall, made its world premiere with a sold-out run at the Signature Theatre in Washington, D.C., from December 9, 2014, to January 25, 2015. She remained part of the production and its extended run when it was staged by the Delaware Theatre Company in December 2015.
Henningsen made her Broadway debut as Fantine in the revival of Les Misérables on March 3, 2015. She has disclosed in interviews that she was about to file for unemployment when she learned she was cast as Fantine, which also happened to be the last role she played as an undergraduate at the University of Michigan, 11 months earlier. She is the youngest actress in Broadway history (to date) to portray the role of Fantine. She left the production along with fellow Les Misérables co-stars Ramin Karimloo and Samantha Hill on August 30, 2015, and was replaced by Memphis star Montego Glover.[20]
In the summer of 2016, Henningsen portrayed Ensign Nellie Forbush, opposite Ben Davis, in the Pittsburgh Civic Light Opera’s production of South Pacific.
In February 2017, she appeared in an Off-Broadway staged concert of Jerry Herman’s musical Dear World as Nina with the York Theatre Company, starring alongside Tyne Daly, Alison Fraser, and Ann Harada.
Henningsen returned to the Pittsburgh Civic Light Opera (PCLO) in the summer of 2017, starring as Sophie in the company’s regional production of Mamma Mia!.[25] During her run at PCLO, it was announced that she was cast as Cady Heron in the upcoming Washington, D.C. production of Mean Girls.
Beginning in 2017, Henningsen starred as Cady Heron in the Tony Award-nominated Broadway musical Mean Girls, written by Tina Fey with music and lyrics by Jeff Richmond and Nell Benjamin, respectively. The show had its world premiere as an out-of-town tryout at the National Theatre in Washington, D.C., from October 31, 2017, to December 3, 2017, in which Henningsen originated the role of Cady Heron. She was later nominated for an Outer Critics Circle Award for this role. The musical, which is based on the film of the same name, began previews on March 12, 2018, and officially opened on Broadway on April 8, 2018, at the August Wilson Theatre in New York City. During the weeks surrounding the Broadway opening of Mean Girls, Henningsen filmed a series of video blogs for Broadway.com entitled “Too Grool for School: Backstage at Mean Girls with Erika Henningsen”, giving viewers a look backstage and at events like opening night, the cast album recording, and the cast’s appearance on The Today Show. Henningsen left the production on February 22, 2020, and was replaced by actress Sabrina Carpenter.
In March 2019, she portrayed Helen, opposite Mean Girls co-star Kyle Selig, in Stephen Sondheim’s Saturday Night at Second Stage Theater as a part of the theater’s “Musical Mondays” weekly concert series.
In December 2022, Henningsen starred as Joy Mangano in the world premiere of the musical Joy at the George Street Playhouse in New Jersey.