Guru Angad was born in a village, with birth name of Lehna, to Hindu parents living in northwestern part of the Indian subcontinent called the Punjab region. He was the son of a small but successful trader named Pheru Mal. His mother's name was Mata Ramo (also known as Mata Sabhirai, Mansa Devi and Daya Kaur). Like all the Sikh Gurus, Lehna came from Khatri caste. Guru Angad Dev ji was born on 31 March 1504.

At age 16, Angad married a Khatri girl named Mata Khivi in January 1520. They had two sons (Dasu and Datu) and one or two daughters (Amro and Anokhi), depending on the primary sources. The entire family of his father had left their ancestral village in fear of the invasion of Babar's armies. After this the family settled at Khadur Sahib, a village by the River Beas near what is now Tarn Taran.

Before his death, Guru Angad, following the Example set by Guru Nanak, nominated Guru Amar Das as his successor (The Third Nanak), instead of choosing his own son. Before he converted to Sikhism, Amar Das had been a religious Hindu (Vaishnava), when one day he heard Bibi Amro, the daughter of Guru Angad singing a hymn by Guru Nanak. Amar Das learnt from her about Guru Angad, and with her help met the second Guru of Sikhism in 1539. From then on, Amar Das renounced his Vaishnava practice and became a disciple of Guru Angad, who was much younger than himself .

The second Mughal Emperor of India Humayun visited Guru Angad around 1540 after Humayun lost the Battle of Kannauj, and thereby the Mughal throne to Sher Shah Suri. According to Sikh hagiographies, when Humayun arrived in Khadur Sahib Guru Angad was sitting and listening to hymns of the sangat. The failure to greet the Emperor immediately angered Humayun. Humayun lashed out but the Guru reminded him that the time when you needed to fight when you lost your throne you ran away and did not fight and now you want to attack a person engaged in prayer. In the Sikh texts written more than a century after the event, Guru Angad is said to have blessed the Emperor, and reassured him that someday he will regain the throne.

Amar Das displayed relentless devotion and Service to Guru Angad, including waking up in the early hours and fetching water for Guru Angad's bath, cleaning and cooking for the volunteers with the Guru, as well devoting much time to meditation and prayers in the morning and evening. Guru Angad named Amar Das as his successor in 1552, instead of naming his surviving son Shri Chand. Guru Angad died on 29 March 1552.