Thomas was a member of Lok Sabha from 9th Lok Sabha to 14th Lok Sabha, serving for 20 years from 1989 to 2009. He was also Union Minister of State for Law and Justice from 2003 to 2004 in the Third Vajpayee Ministry.

His first contest in General election was in 1987, from Vazhoor Legislate Assembly Constituency, which he lost. Later in 1989 he contested in the Lok Sabha election from Muvattupuzha as the candidate of Kerala Congress (M) and defeated Left Democratic Front (LDF) candidate P. P. Esthos and P. J. Joseph, another Kerala Congress leader. He won all subsequent election from the constituency till 2009. His contest in 2004 as the candidate of National Democratic Alliance (NDA), where he defeated both the candidates of United Democratic Front (UDF) and Left Democratic Front (LDF), was considered a landmark victory in the political history of Kerala.^[2] However, Supreme Court of India cancelled the results and disqualified him in 2006 on the ground that he used his religious background to woo voters during the polls.^[3]

In 1986, P. C. Thomas was chosen to serve on Kerala's 6th Bar Council.

After his Lok Sabha term, he has filed about 15 public interest litigations as part-in-person, in the High Court of Kerala and Supreme Court of India

In 2006, when Finance Minister P. Chidambaram made an announcement that the Government of India will issue a commemorative coin dedicated to the 150th anniversary of Sree Narayana Guru, P. C. Thomas suggested that coin' logo should be written both in Hindi and English.^[4]

Since 2010, Thomas is the chairman of Kerala Congress (Thomas). Currently the party is in alliance with National Democratic Alliance (NDA), of which he is a National Committee member. He is also the Chairman of ‘Karshaka Sanghatana Aikyavedi’, a farmers' non-political organization which is a platform of several associations of various types of farmers’ organizations in Kerala including those of natural rubber farmers.^[5]

In 2019, P. C. Thomas ran for election again,^[5] this time from Kottayam Lok Sabha constituency, however he came third in the election which was won by Thomas Chazhikadan of Kerala Congress (Mani).

On 17 March 2021, he announced that his party has left NDA alliance and joined UDF. The party would merge with P.J. Joseph led-Kerala Congress (Joseph) and form Kerala Congress.^[6]

P. C. Thomas is the fourth child of P. T. Chacko and Mariyamma Chacko. Pullolil House is his residence. His father P. T. Chacko was a political stalwart who was a member of Indian Constituent Assembly representing Travancore-Cochin from 1949, a member representing Meenachil Lok Sabha Constituency in the first Lok Sabha in 1952, first opposition leader of the Kerala Legislative Assembly in 1957 and the Home Minister in Pattom Thanu PillaiI's ministry. Thomas has two sons and a daughter.