Lakecia Benjamin was born and raised in Washington Heights, a predominantly Dominican neighborhood in upper Manhattan. Her first music was Latin dance music: she played merengue and salsa, learned the recorder in grade school and junior high, and began writing songs and lyrics at 13. She earned a place at Fiorello H. LaGuardia High School for the Performing Arts, where she took up the saxophone in earnest, and went on to the jazz program at The New School. There she studied with Billy Harper, Reggie Workman, Buster Williams, Joe Chambers and Gary Bartz. Bartz became her most important mentor, drilling her in technical exercises such as Hyacinthe Klosé's daily etudes and steering her toward the playing of Charlie Parker, John Coltrane and Jackie McLean.

Her first job was in the Young Titans of Jazz, a band of students of Clark Terry; she plays alto saxophone on its live album from Marians Jazzroom in Bern, recorded on May 2, 2004. She then spent years as a New York sideperson and horn-section leader across jazz, soul, funk and pop, working with Rashied Ali, the David Murray Big Band, James Blood Ulmer, the Count Basie Orchestra, Gregory Porter, Anita Baker, The Roots, Missy Elliott, Alicia Keys and Stevie Wonder, and playing at President Barack Obama's 2009 inauguration. She is also among the younger players the Harlem saxophonist Bill Saxton is said to have brought up on his bandstand at Bill's Place. She formed her own band, Soul Squad, to play her compositions, and made her debut as a leader with Retox (Motéma, 2012), a set of soul and funk originals and covers produced by Ben Kane, with guests including Krystle Warren, Amp Fiddler, Maya Azucena and Melanie Charles. In 2016 she played on "Right On Brotha," the closing track of Robert Glasper's Everything's Beautiful, a project built on reworked Miles Davis recordings. Her second album, Rise Up (Ropeadope, March 23, 2018), was a set of original jazz-funk pieces for a rhythm section, horns and a cast of vocalists.

Her breakthrough came with Pursuance: The Coltranes, a tribute to John Coltrane and Alice Coltrane. She previewed it at Winter Jazzfest on January 11, 2020, at Le Poisson Rouge in Manhattan, with Reggie Workman, Marcus Strickland, Greg Osby and Regina Carter joining her, and Ropeadope released it on March 27, 2020. It has thirteen tracks, seven by John Coltrane and six by Alice, and draws on more than forty musicians across three generations, among them Ron Carter, Gary Bartz, Dee Dee Bridgewater, Regina Carter, Meshell Ndegeocello, Steve Wilson, Marc Cary, Keyon Harrold, Brandee Younger and Jazzmeia Horn. Workman is credited as co-producer, and the poet Abiodun Oyewole speaks on "Acknowledgement." The band name Pursuance comes from the album title, and the word is also the title of the third part of Coltrane's A Love Supreme, a piece she recorded as track 11 of the album. Her touring band for this repertoire is billed as Lakecia Benjamin and Pursuance (a 2022 Penn Live Arts program, for example, paired the band with Dee Dee Bridgewater and Gary Bartz), while her own tour calendar bills other eras differently: Soul Squad for the early funk-and-soul band, and Lakecia Benjamin and Phoenix for the later band behind her 2023 album. In 2020 she was named Rising Star alto saxophonist in the DownBeat Critics Poll and received the Jazz Journalists Association's Up and Coming Artist of the Year award.

In September 2021 she was seriously injured in a single-car accident, with injuries that included a broken jaw, after driving home from a festival concert in Cleveland, and she has described the recovery as the root of her next record. Phoenix (Whirlwind Recordings, January 27, 2023) was produced by Benjamin and Terri Lyne Carrington. It features her working band of pianist Victor Gould, bassist Ivan Taylor and drummer E.J. Strickland, trumpeter Josh Evans on most tracks, and guests including Dianne Reeves on "Mercy," Patrice Rushen on "Jubilation," and Georgia Anne Muldrow on the title track, with spoken-word contributions from Angela Davis, Sonia Sanchez and Wayne Shorter. It earned three nominations at the 66th Annual Grammy Awards: Best Jazz Instrumental Album, Best Jazz Performance for "Basquiat," and Best Instrumental Composition for "Amerikkan Skin." The live album Phoenix Reimagined, recorded on March 2, 2024, at Bunker Studios in Brooklyn and released by Ropeadope on July 12, 2024, drew two more nominations at the 67th Grammys, for Best Jazz Instrumental Album and, with guests Randy Brecker, Jeff "Tain" Watts and John Scofield, Best Jazz Performance. NPR Music published her Tiny Desk concert on June 5, 2024. Her single "Noble Rise," featuring Immanuel Wilkins and Mark Whitfield, came out on June 27, 2025, and was nominated for Best Jazz Performance at the 68th Grammys. By Grammy.com's count she has six nominations and no wins.

We Dream, her sixth album and first for Artwork Records, was released on June 5, 2026. It features her band of pianists Oscar Pérez and Miki Hayama, bassist Elias Bailey, trumpeter Sean Jones and drummer Jonathan Barber, with guests including Terence Blanchard, Chief Xian aTunde Adjuah, Chris Potter, Jeff "Tain" Watts, Hiromi Uehara, Black Thought, Bilal, Tarriona "Tank" Ball and Kassa Overall. She has described it as a response to the current state of the world, and it mixes spoken word, groove-based writing and long improvisations.

Benjamin plays a warm, resonant alto that AllMusic compares to Johnny Griffin's, and her records move between jazz, funk, soul, R&B and hip-hop without treating them as separate worlds. Her roots in Latin dance music and the years spent leading horn sections for soul and pop singers explain why her albums lean on groove as much as on solos. Gary Bartz gave her the saxophone tradition running from Charlie Parker to John Coltrane, and the Coltranes are her central reference: she discovered the music of Alice Coltrane before John's, through a friend, and came to see the two as complementary, which shaped Pursuance: The Coltranes and the Pursuance concert programs. Her working method on the larger projects is the guest-filled record that puts several generations of players together, with Workman, Carter and Bartz beside younger musicians on Pursuance and Reeves, Rushen and Shorter's voice on Phoenix, produced alongside Terri Lyne Carrington. DownBeat and the Jazz Journalists Association honored her in 2020, and her six Grammy nominations between 2024 and 2026 place her among the most visible alto saxophonists of her generation in New York jazz.