Mani started her career as a video jockey before moving on to hosting. She co-hosted the Hum 2 Hamara Show on Hum TV with Mani, which earned her critical recognition, and they both followed it with the Hira Mani Show (2010). Hira made her acting debut along with her husband Mani in ARY Digital's Meri Teri Kahani (2012). The show was inspired by the American series Curb Your Enthusiasm. Both (Mani and Hira) appeared as fictionalized versions of themselves. She then appeared as Heer in Jab We Wed (2013) and as Hareem in Firaaq (2013). In 2015, she portrayed the role of Shagufta in Hum TV's Preet Na Kariyo Koi opposite Ahsan Khan. She received critical praise for portraying an emotionally intense character in the serial. She later appeared as a guest in Mr. Shamim (2016) and Kitni Girhain Baaki Hain 2 (2016). Her stint in hit TV series, Mere Paas Tum Ho was critically acclaimed. The TV series also featured Humayun Saeed, Adnan Siddiqui, and Ayeza Khan in lead roles.
Hira married fellow actor Salman Saqib Sheikh (Mani) at the age of 19. Their marriage ceremony took place on 18 April 2008. They frequently work together in most of their projects. The couple has two sons, Muzammil (born in 2009) and Ibrahim (born in 2014). In May 2021, Hira was mugged outside her home in Karachi, the video of which went viral.