She started training in martial arts at a young age, beginning at 6 with Shaolin Kung Fu under the tutelage of a local master, after she was inspired by Kung Fu films. In primary school, she practiced many sports including athletics, football and table tennis. When she was 12, her parents sent her to a specialized martial arts school in Handan where she began training in Sanda and a Chinese style of wrestling called Shuai jiao.After winning Sanda championships of the Hebei province multiple times, she was selected for the Jiangsu province Sanda team, however a recurring back injury sustained in training forced her to quit the sport early.

At the age of 17 she moved to Beijing, where she worked various odd jobs: cashier at a supermarket, kindergarten teacher, security guard and hotel desk clerk. In 2010 she found a job at a local Beijing gym as a fitness instructor, and was allowed to use their equipment for free after the gym closed in the evenings. During that time she would also pick up Brazilian jiu-jitsu, after watching others grappling there. She later switched to a front desk job, through which she got to know fighters who trained at the gym, one of them being her idol Wu Haotian, a pioneer of Chinese MMA. After they became acquainted in 2012, Haotian brought her to Black Tiger Fight Club. There, she was noticed by coach Cai Xuejun, who recognized her potential and started training her in MMA.

In a Chinese television show in December 2019, she mentioned that Hong Kong Action Superstar Donnie Yen was her inspiration to compete in MMA, and that Donnie Yen's 2007 feature film Flashpoint was her first introduction to the sport of MMA. She also credited Ronda Rousey, and particularly her fight with Liz Carmouche in 2013, as giving her the motivation to quit her job and pursue MMA full-time.

Zhang made her first title defense against Aline Sattelmayer on June 1, 2017, at Kunlun Fight MMA 12. She won the fight by unanimous decision.

On July 22, 2017, Zhang attempted to win a second title, when she challenged Seo Ye-dam (서예담) for the vacant Top FC Strawweight Championship at TOP FC 15. She won the fight via TKO in the second round to capture the title.

In her next bout, Zhang made her second KLF title defense on August 28, 2017, at Kunlun Fight MMA 14 against Marilia Santos. She won the fight via TKO in the second round.

Zhang would fight one more time for KLF, amassing a record of 16–1 and improving her winning streak to 16 before signing with the UFC.

Zhang made her promotion debut on August 4, 2018, at UFC 227 against Danielle Taylor. She won the fight via unanimous decision.

On November 24, 2018, Zhang faced Jessica Aguilar at UFC Fight Night: Blaydes vs. Ngannou 2. She won the fight via a submission in round one.

Zhang faced Tecia Torres on March 3, 2019, at UFC 235.She won the fight via unanimous decision.

Zhang faced Jéssica Andrade for the UFC Women's Strawweight Championship on August 31, 2019, at UFC Fight Night 157. She won the fight via first-round technical knockout to become the new strawweight champion, and the first UFC champion from China. The win also earned Zhang her first Performance of the Night bonus award.

In the first defense of her title, Zhang faced former strawweight champion Joanna Jędrzejczyk on March 7, 2020, at UFC 248. Zhang moved her training camp from China to Thailand and later moved to Dubai due to the COVID-19 pandemic,as TSA rules stated a two-week quarantine was imposed for any non-US citizen be granted entry to the United States if they had recently been in China.[34] After multiple failed attempts to obtain a US visa to fight in UFC's events in the US, on February 19, 2020, Zhang was granted US visa to fight at UFC 248. Zhang won the back–and–forth fight via split decision, which marked her first successful title defense.This win also marked her first Fight of the Night award. This bout was considered by many pundits as the greatest fight in women's MMA history.

In the second defense of her title, Zhang faced former strawweight champion Rose Namajunas on April 24, 2021, at UFC 261. She lost the fight by knockout early in the first round after getting caught with a head kick.

A rematch between Zhang and Namajunas for the UFC Women's Strawweight Championship took place on November 6, 2021, at UFC 268.[44] After a back and forth bout, Weili lost the fight via split decision. 14 out of 22 media scores gave it to Namajunas.

A rematch between Zhang and Joanna Jędrzejczyk took place on June 11, 2022, at UFC 275.For this fight Zhang trained at Bangtao Muay Thai & MMA gym in Thailand and worked with Josh Hinger.Zhang won the fight via knockout with a spinning backfist in the second round.This win earned her the Performance of the Night award and the Crypto.com "Fan Bonus of the Night" awards paid in bitcoin of US$10,000 for third place.

Zhang faced reigning champion Carla Esparza for the UFC Women's Strawweight Championship on November 12, 2022, at UFC 281. Zhang won the bout and regained the championship by the way of a rear-naked choke submission in the second round.This win earned her the Performance of the Night award. Zhang was promoted to brown belt in Brazilian Jiu-Jitsu following her win.

Zhang next defended her title against Amanda Lemos on August 19, 2023, at UFC 292.She defeated Lemos via unanimous decision after a dominant performance, with Zhang out striking Lemos 296-29, the largest differential for a women's fight in UFC history.The emphatic win also earned Zhang her fourth Performance of the Night award.

• Ultimate Fighting Championship
  • UFC Women's Strawweight Championship (Two times, Current)
    • Two successful title defenses (Overall)
      • One successful title defense (First reign)
      • One successful title defense (Second reign)
    • Tied (Rose Namajunas) for second most title fight wins in UFC Women's Strawweight division history (4)
    • First ever Chinese champion in UFC history
  • Fight of the Night (One time) vs. Joanna Jędrzejczyk 1
    • UFC Honors 2020 Fight of the Year vs. Joanna Jędrzejczyk 1
    • UFC.com 2020 Fight of the Year vs. Joanna Jędrzejczyk 1
  • Performance of the Night (Four times) vs. Jéssica Andrade, Joanna Jędrzejczyk 2, Carla Esparza & Amanda Lemos
    • UFC Honors 2022 Performance of the Year vs. Joanna Jędrzejczyk 2
    • 2022 Half-Year Awards: Best Knockout of the 1HY vs. Joanna Jędrzejczyk 2
    • Fourth most Post-Fight bonuses in UFC Women's Strawweight division history (5)
  • Largest striking differential in a bout in UFC Women's history (288:21) (vs. Amanda Lemos)
  • Most significant ground strikes landed in a UFC Women's Strawweight bout (96) (vs. Amanda Lemos)
    • Most total ground strikes landed in a UFC Women's Strawweight bout (225) (vs. Amanda Lemos)
  • Most total strikes landed in a UFC Women's Strawweight bout (296) (vs. Amanda Lemos)

• Kunlun Fight
  • KLF Female Strawweight Champion (One time)
    • Two successful title defenses
• Top Fighting Championship
  • Top FC Strawweight Champion (One time)
• MMAJunkie.com
  • 2020 March Fight of the Month vs. Joanna Jędrzejczyk
  • 2020 Fight of the Year vs. Joanna Jędrzejczyk
  • 2022 June Knockout of the Month vs. Joanna Jędrzejczyk
  • 2022 November submission of the Month vs. Carla Esparza
  • 2022 Female Fighter of the Year
  • 2022 Comeback Fighter of the Year
• World MMA Awards
  • 2019 – July 2020 Fight of the Year vs. Joanna Jędrzejczyk at UFC 248
• Wrestling Observer Newsletter
  • 2020 MMA Match of the Year vs. Joanna Jędrzejczyk
  • Women's MMA MVP (2022)
• MMA Fighting
  • 2020 Fight of the Year vs. Joanna Jędrzejczyk
• The Athletic
  • 2020 Fight of the Year vs. Joanna Jędrzejczyk
• Bleacher Report
  • 2020 Fight of the Year vs. Joanna Jędrzejczyk
• Cageside Press
  • 2020 Fight of the Year vs. Joanna Jędrzejczyk
  • 2022 Female Fighter of the Year^[85]
• Sherdog
  • 2020 Fight of the Year vs. Joanna Jędrzejczyk
• BT Sport
  • 2020 Fight of the Year vs. Joanna Jędrzejczyk
  • 2022 Female Fighter of the Year
• MMA Weekly
  • 2020 Fight of the Year vs. Joanna Jędrzejczyk
• Combat Press
  • 2020 Fight of the Year vs. Joanna Jędrzejczyk
• ESPN
  • 2022 Female Fighter of the Year