Serena Brancale was born in Bari on May 4, 1989. Her mother ran a music school and started her on violin and piano as a child. She studied advertising graphics at the Accademia di Belle Arti di Bari, then took a degree in jazz singing at the Conservatory of Bari, and she moved to Rome at 26. At fourteen she had played Annamaria in Alessandro Piva's film Mio cognato (2003), and she was turned down at the 2009 X Factor auditions before music became her working life.

Her first jazz-room credits come before her pop career. On Italian Bossa Bar (2010, Azzurra Music), a bossa nova album credited to Marchio Bossa, she sings three of the twelve tracks beside Francesca Leone, in a band that includes saxophonist Daniele Scannapieco and guitarist Guido Di Leone. In 2011 she founded the Serena Branquartet and released a self-issued live CD, Serena Brancale Live, whose ten tracks include "Goodbye Pork Pie Hat" and "Chameleon", the titles of well known pieces by Charles Mingus and Herbie Hancock, next to original songs. Discogs files the record under Jazz and Funk / Soul, and event listings of the period placed the quartet halfway between nu soul and jazz.

In 2015 she entered the newcomers' section of the Sanremo Music Festival with "Galleggiare" and was eliminated in a head-to-head vote with Giovanni Caccamo, the eventual winner. The album Galleggiare followed on February 25, 2015 (Warner Music Italy), with trumpeter Fabrizio Bosso on flugelhorn and pianist Mirko Signorile on the title track. In 2016 she made her American debut at New York University's Casa Italiana Zerilli-Marimò on March 21, and on December 12 she opened the Nomos Jazz season at the Teatro Jolly in Palermo in a jazz and soul program with singer Walter Ricci and pianist Domenico Sanna. In 2017 she took part in Mario Biondi's Best of Soul Tour. In 2018 she signed with the label Isola degli Artisti and, according to Italian Wikipedia, began teaching composition, arrangement and pop singing at the Saint Louis College of Music in Rome.

Her second studio album, Vita da artista (2019), leaned toward neo soul and carried guest spots by Willie Peyote and Mama Marjas. In January 2022 a video of her Pino Daniele cover "Je so' pazzo", reworked with the Cameroonian bassist and singer Richard Bona, opened with a spoken endorsement from Quincy Jones, and the album Je sò accussì appeared on March 25, 2022. It is a funk and neo soul record with Bona on "Je so' pazzo", Bosso on trumpet for the Margherita Vicario duet "Donna", and further appearances by Ghemon, Davide Shorty and Roshelle. In 2023 she was announced as the first woman on the bill of the 36th Time in Jazz festival, directed by Paolo Fresu in Berchidda, with a one-woman "Soula" set built on piano, loop station and electronic drums. Italian Wikipedia also lists a 2023 career prize from Salerno Jazz. On July 7, 2025 she played the Blue Note in New York for the first time, after earlier dates at clubs in Tokyo, Shanghai and Seoul.

The larger public came through the pop side. "Baccalà" (February 2024), a Barese-dialect single made with the producer Dropkick_m, went viral in Italy. In 2025 she returned to Sanremo in the main competition with "Anema e core", the first Sanremo entry sung in Barese, which placed 24th and later went platinum, and she followed it with "Serenata", a duet with Alessandra Amoroso that reached No. 3 on the Italian singles chart. At Sanremo 2026 she placed ninth with "Qui con me" and won three of the festival's side awards. On the cover night, February 27, 2026, she sang "Bésame mucho" with Gregory Porter and the singer Delia, and her fourth studio album, Sacro, followed on April 10, 2026 (Atlantic Records Italy), with Bona as a producer and guest and Porter, Omara Portuondo and Alborosie among the other voices. Her recorded catalog is mainly pop, funk and neo soul, and AllMusic files her under Pop/Rock; the jazz side lives in her training, her stage bookings and her guest list.

Brancale is a conservatory-trained jazz singer who built her career on pop, funk and neo soul, and she says plainly that she resists strict genre labels. She sings in Italian and in Barese dialect over funk and neo soul grooves with trumpets, finger drumming and electronics, and her live "one girl band" format uses piano and a loop station. Ahead of the Blue Note date she named Ray Charles and Ella Fitzgerald among the idols who had played that stage, and she credits Pino Daniele, the Neapolitan singer-songwriter whose blend of blues, soul and Mediterranean song runs through Je sò accussì, as a defining sound. She has described her approach on Sacro as jazz-inspired, a way of mixing styles more internationally. The jazz connection is therefore documented but partial: a jazz degree, a quartet live album with jazz repertoire, a bossa nova session with jazz players, and bookings at jazz festivals and clubs, set against a catalog that critics and databases file mostly under pop and soul.