Mirza Ghalib was born in Agra into a family descended from Aibak Turks who moved to Samarkand after the downfall of the Seljuk kings. His paternal grandfather, Mirza Qoqan Baig Khan was a Saljuq Turk who had immigrated to India from Samarkand (now in Uzbekistan) during the reign of Ahmad Shah (1748–54). He worked at Lahore, Delhi and Jaipur, was awarded the subdistrict of Pahasu(Bulandshahr, UP) and finally settled in Agra, UP, India. He had 4 sons and 3 daughters. Mirza Abdullah Baig Khan and Mirza Nasrullah Baig Khan were two of his sons. Mirza Abdullah Baig Khan (Ghalib's father) got married to Izzat-ut-Nisa Begum, and then lived at the house of his father in law. He was employed first by the Nawab of Lucknow and then the Nizam of Hyderabad, Deccan. He died in a battle in 1803 in Alwar and was buried at Rajgarh (Alwar, Rajasthan).  Then Ghalib was a little over 5 years of age. He was raised first by his Uncle Mirza Nasrullah Baig Khan.  Mirza Nasrullah Baig Khan (Ghalib's uncle) started taking care of the three orphaned children. He was the governor of Agra under the Marathas. The British appointed him an officer of 400 cavalrymen, fixed his salary at Rs.1700.00 month, and awarded him 2 parganas in Mathura (UP, India). When he died in 1806, the British took away the parganas and fixed his pension as Rs. 10,000 per year, linked to the state of Firozepur Jhirka (Mewat, Haryana). The Nawab of Ferozepur Jhirka reduced the pension to Rs. 3000 per year. Ghalib's share was Rs. 62.50 / month. Ghalib was married at age 13 to Umrao Begum, daughter of Nawab Ilahi Bakhsh (brother of the Nawab of Ferozepur Jhirka). He soon moved to Delhi, along with his younger brother, Mirza Yousuf Khan, who had developed schizophrenia at a young age and later died in Delhi during the chaos of 1857.

In accordance with upper class Muslim tradition, he had an arranged marriage at the age of 13, but none of his seven children survived beyond infancy. After his marriage he settled in Delhi. In one of his letters he describes his marriage as the second imprisonment after the initial confinement that was life itself. The idea that life is one continuous painful struggle which can end only when life itself ends, is a recurring theme in his poetry. One of his couplets puts it in a nutshell:

Being as a member of declining Mughal nobility and old landed aristocracy, he never worked for a livelihood, lived on either royal patronage of Mughal Emperors, credit or the generosity of his friends. His fame came to him posthumously. He had himself remarked during his lifetime that although his age had ignored his greatness, it would be recognized by later generations. After the decline of Mughal Empire and rise of British Raj, despite his many attempts, Ghalib could never get the full pension restored.

Although Ghalib himself was far prouder of his poetic achievements in Persian,  he is today more famous for his Urdu ghazals. Numerous elucidations of Ghalib's ghazal compilations have been written by Urdu scholars. The first such elucidation or Sharh was written by Ali Haider Nazm Tabatabai of Hyderabad during the rule of the last Nizam of Hyderabad. Before Ghalib, the ghazal was primarily an expression of anguished love; but Ghalib expressed philosophy, the travails and mysteries of life and wrote ghazals on many other subjects, vastly expanding the scope of the ghazal. This work is considered his paramount contribution to Urdu poetry and literature.

In keeping with the conventions of the classical ghazal, in most of Ghalib's verses, the identity and the gender of the beloved is indeterminate. The critic/poet/writer Shamsur Rahman Faruqui explains  that the convention of having the "idea" of a lover or beloved instead of an actual lover/beloved freed the poet-protagonist-lover from the demands of realism. Love poetry in Urdu from the last quarter of the seventeenth century onwards consists mostly of "poems about love" and not "love poems" in the Western sense of the term.

The first complete English translation of Ghalib's ghazals was written by Sarfaraz K. Niazi  

 Mirza Ghalib was a gifted letter writer.  Not only Urdu poetry but the prose is also indebted to Mirza Ghalib. His letters gave foundation to easy and popular Urdu. Before Ghalib, letter writing in Urdu was highly ornamental. He made his letters "talk" by using words and sentences as if he were conversing with the reader. According to him Sau kos se ba-zaban-e-qalam baatein kiya karo aur hijr mein visaal ke maze liya karo (from hundred of miles talk with the tongue of the pen and enjoy the joy of meeting even when you are separated). His letters were very informal, some times he would just write the name of the person and start the letter. He himself was very humorous and also made his letter very interesting. He said Main koshish karta hoon keh koi aesi baat likhoon jo parhay khoosh ho jaaye (I want to write the lines that whoever reads those should enjoy it). When the third wife of one of his friends died, he wrote. Some scholar says that Ghalib would have the same place in Urdu literature if only on the basis of his letters. They have been translated into English by Ralph Russell, The Oxford Ghalib.

His original Takhallus (pen-name) was Asad, drawn from his given name, Asadullah Khan. At some point early in his poetic career he also decided to adopt the Takhallus Ghalib (meaning all conquering, superior,most excellent).

Popular legend has it that he changed his pen name to 'Ghalib' when he came across this sher (couplet) by another poet who used the takhallus (pen name) 'Asad':

The legend says that upon hearing this couplet, Ghalib ruefully exclaimed, "whoever authored this couplet does indeed deserve the Lord's rahmat (mercy) (for having composed such a deplorable specimen of Urdu poetry). If I use the takhallus Asad, then surely (people will mistake this couplet to be mine and) there will be much la'anat (curse) on me!" And, saying so, he changed his takhallus to 'Ghalib'.

However, this legend is little more than a figment of the legend-creator's imagination. Extensive research performed by commentators and scholars of Ghalib's works, notably Imtiyaz Ali Arshi and Kalidas Gupta Raza, has succeeded in identifying the chronology of Ghalib's published work (sometimes down to the exact calendar day!). Although the takhallus 'Asad' appears more infrequently in Ghalib's work than 'Ghalib', it appears that he did use both his noms de plume interchangeably throughout his career and did not seem to prefer either one over the other.

The poem was unexpected, but it came at the time when Syed Ahmad Khan’s thought and feelings themselves were inclining toward change. Ghalib seemed to be acutely aware of a European[English]-sponsored change in world polity, especially Indian polity. Syed Ahmad might well have been piqued at Ghalib’s admonitions, but he would also have realized that Ghalib’s reading of the situation, though not nuanced enough, was basically accurate. Syed Ahmad Khan may also have felt that he, being better informed about the English and the outside world, should have himself seen the change that now seemed to be just round the corner  Sir Syed Ahmad Khan never again wrote a word in praise of the Ai’n-e Akbari and in fact gave up   taking active interest in history and archaeology, and became a social reformer.

Mirza was born in Kala Mahal in Agra. In the end of 18th century, his birthplace was converted into Indrabhan Girls' Inter College. The birth room of Mirza Ghalib is preserved within the school. Around 1810, he was married to Umrao Begum, daughter of Nawab Ilahi Bakhsh Khan of Loharu (younger brother of the first Nawab of Loharu, Nawab Mirza Ahmad Baksh Khan,  at the age of thirteen. He had seven children, none of whom survived (this pain has found its echo in some of Ghalib's ghazals). There are conflicting reports regarding his relationship with his wife. She was considered to be pious, conservative and God-fearing.

He died in Delhi on February 15, 1869. The house where he lived in Gali Qasim Jaan, Ballimaran, Chandni Chowk, in Old Delhi has now been turned into 'Ghalib Memorial' and houses a permanent Ghalib exhibition.

Ghalib's closest rival was poet Zauq, tutor of Bahadur Shah Zafar II, the then emperor of India with his seat in Delhi. There are some amusing anecdotes of the competition between Ghalib and Zauq and exchange of jibes between them. However, there was mutual respect for each other's talent. Both also admired and acknowledged the supremacy of Meer Taqi Meer, a towering figure of 18th century Urdu Poetry. Another poet Momin, whose ghazals had a distinctly lyrical flavour, was also a famous contemporary of Ghalib. Ghalib was not only a poet, he was also a prolific prose writer. His letters are a reflection of the political and social climate of the time. They also refer to many contemporaries like Mir Mehdi Majrooh, who himself was a good poet and Ghalib's life-long acquaintance.Indian Cinema has paid a tribute to the legendary poet through a film  named Mirza Ghalib (1954) in whichBharat Bhushan plays Ghalib and Suraiya plays his courtesan lover, Chaudvin. The musical score of the film was composed by Ghulam Mohammed and his compositions of Ghalib's famous ghazals are likely to remain everlasting favorites.