Palijo's mother was the Baloch women's rights activist, writer and artist, Jeejee Zarina Baloch. His father was Rasool Bux Palijo, the Sindhi leftist founder of Awami Tahreek.
Palijo was educated at the Model School, Old-campus, Sindh University, Hyderabad. In his teenage years, under his mother's guidance, Palijo studied Sindhi, Balochi and Urdu. He later became conversant in English, Seraiki, Punjabi and Persian.
At age eleven, Palijo was central secretary general of the Gulan Jahra Barira and the Sujag Bar Tahreek, the children's wing of the Awami Tahreek. He was then a university student activist.
Palijo received a degree in civil engineering from Mehran University of Engineering and Technology, Jamshoro, and a degree in law from Sindh University, Jamshoro. He received a degree in environment and development from the University of British Columbia, Vancouver, British Columbia, Canada. Palijo also received a postgraduate degree in rural development from Sindh University and Wye College, United Kingdom.
Palijo received a LEAD (leadership in educational administrate doctorate) in the seventh cohort.
Palijo is a constitutional lawyer of Sindh High Court. He led the movement that culminated in the restoration of the Chief Justice, Iftikhar Mohammad Chaudhry.
Palijo is the president of Awami Tahreek (Peoples Movement) and central convener and founder of the Sindh Progressive Nationalist Alliance (SPNA). He said,
"Today Sindh is passing famine like situation. Conspiracies are being made for disintegration of Sindh and Pakistan. People are committing suicide and selling their children due man-made price hike, water-shortage, crimes and corruption. We'll die but we won't let Sindh be divided, How long the rulers embroil the people of Sindh in concocted stories? People are full of hatred and warmly contributing their part in struggle. Hugely participation of public and political groups irrespective of socio-political and religious affiliations proved that Sindh is united."
In 2013, Palijo opposed the building of the Kalabagh Dam.
In May 2012, Awami Tehrik Party members and workers organised a rally in Karachi to protest the formation of the Mohajir province (Lyari Mohajir Suba Na-manzoor).
In 2012, women were able to attend Muhabat-e-Sindh (Love of Sindh) rally in equal numbers to men. The marchers were attacked near Nawa Lane, Pan Mandi and Juna Market. Eleven people were killed and about thirty were injured. Palijo announced to the press a peaceful strike in Sindh to highlight the incident and said his party would stage a sit-in protest till the attackers were apprehended.
On Saturday, 14 July 2012, two months after the anti-Mohajir rally, Palijo announced that a Shaheedan-e-Muhabbat-e-Sindh Jalsa would take place on Sunday, 15 July at Gabol Park, Lyari. In his speech, Palijo said, "Nobody can stop us from entering Lyari and other parts of Karachi." Palijo criticised the Sindh Government, saying that 4000 policemen were deployed by the Sindh government to stop his rally. After the announcement, the Sindh home minister ordered Palijo's arrest and Palijo received threats of attacks.
On 11 May 2013, a general election took place. Palijo was a candidate for PS-47 Qasimabad, Hyderabad constituency. Palijo lost the contest with 14,901 votes. Palijo challenged the result in the Sindh High Court and asked for a re-election. He claimed his agents at the polling booths had been harassed.
On 4 January 2014, Altaf Hussain the Muttahida Qaumi Movement (M.Q.M.) called for a separate province. The PPP chairman Bilawal Bhutto} disagreed. Palijo also disagreed and threatened strikes and protests. Two days later the M.Q.M sent a delegation under Wasim Akhtar to discuss the matter with Palijo. Palijo called off the strikes and protests.