After college, he joined Kalabhavan, a professional mimicry troupe in
Kochi. At the age of 22, he was introduced to the cinema by
script writer and filmmaker
Padmarajan who gave Jayaram a launch pad with the 1988 film
Aparan. Jayaram subsequently acted in Padmarajan's
Moonnam Pakkam (1988) and
Innale (1989). Padmarajan became his
mentor in his film career until the former's death in January 1991. He is noted for appearing in
Kamal's films during the late 1980s and early 1990s, in films such as
Pradeshika Varthakal (1989),
Peruvannapurathe Visheshangal (1989) and
Shubha Yathra (1990) (all of which scripted by
Ranjith), where he co-starred with his wife
Parvathy. He later did a film scripted by Ranjith with the story by
Jagathy Sreekumar and directed by
Viji Thampi named
Witness (1988). He teamed up with Viji Thampi and Ranjith in
Nanma Niranjavan Srinivasan (1990), where he played a police constable who is in search of a criminal played by
Mukesh. During the early '90s he acted in
Bharathan's
Keli (1991) and
Malootty (1992). He has acted in several of
Sathyan Anthikkad's films. Their first film was
Ponmuttayidunna Tharavu (1988). Around that time, Jayaram played a
supporting role in Sathyan Anthikkad's
Artham (1989).
Thalayanamanthram (1990) and
Sandesham (1991), were both written and co-starred
Sreenivasan. Anthikkad and Jayaram later went on to make
Thooval Kottaram (1996), which was a commercial success, continued their success in films -
Irattakuttikalude Achan (1997),
Veendum Chila Veettukaryangal (1999),
Kochu Kochu Santhoshangal (2000),
Yathrakarude Sradhakku (2002),
Manassinakkare (2003),
Bhagya Devatha and
Kadha Thudarunnu. He regularly ensured K.P.A.C Lalitha, Unnikrishnan and Jagathy Sreekumar were cast in his films. He acted in a leading role along with
Mammootty and
Suresh Gopi in
Joshi's
Dhruvam (1993). Other films with Gopi include Viji Thampi's
Nagarangalil Chennu Raparkam (1990),
Thooval Sparsam (1990),
Jayaraj's
Paithrukam (1993), and
Sibi Malayil's
Summer in Bethlehem (1998). He co-starred with
Mohanlal in
Bharath Gopi's
Ulsavapittennu,
Peruvannapurathe Visheshangal (1989) and
Priyadarshan's
Advaitham (1991). His association with director Rajasenan created many movies such as
Kadinjool Kalyanam (1991),
Ayalathe Addeham (1992),
Meleparambil Aanveedu (1993),
CID Unnikrishnan B.A., B.Ed. (1994),
Aniyan Bava Chetan Bava (1995),
Aadyathe Kanmani (1995),
Swapna Lokathe Balabhaskaran (1996), and
Kadhanayakan (1997). He also played Aravindan in
Siddique's
Friends (1999) in which he co-starred with
Sreenivasan and
Mukesh was the highest grossing Malayalam movie of 1999 and collected 11 crore. In the first decade of the 21st century his commercial successful films include
Kochu Kochu Santhoshangal (2000),
Yathrakarude Sradhakku (2002),
Ente Veedu Appuvinteyum (2003),
Manassinakkare (2003),
Veruthe Oru Bharya (2008). His critically acclaimed roles include Karunakaran in B. Kannan's
Theerthadanam (2001) and Lonappan in Rajeev Kumar's
Sesham (2002). He also forayed into
Tamil cinema including roles in
Gokulam,
Purushalakshanam,
Priyanka,
Kolangal,
Murai Mamman and
Pathini. He played the roles of Dr Kailash and Ayyappan Nair in the Kamal Haasan-starred
Thenali and
Panchathanthiram. They first came together on-screen in
Chanakyan (1989). Recently he has done more supporting roles in Tamil, such as
antagonist roles in
Saroja and
Dhaam Dhoom, and a comic role in
Aegan. His movies include
Manassinakkare (2003),
Njaan Salperu Raman Kutty (2004),
Finger Print (2005),
Alice in Wonderland (2005),
Madhuchandralekha (2006),
Moonnamathoral (2006), and
Anchal Oral Arjunan (2007). In mid-2008, he played Sugunan in Akku Akbar's
Veruthe Oru Bharya (2008) and
Thuppakki (2012), which established him as one of the leading comedy actors of
Malayalam and
Tamil films. In 2008, he made a comeback after a series of commercial flops with the film
Veruthe Oru Bharya (2008), which was both a critical and commercial success at the box office and ran for over 100 days in theatres. In 2009, he performed in Sathyan Anthikkad's
Bhagyadevatha, a commercial success and in 2010 his first film was
Happy Husbands, commercial success with 150 days theatrical run, and next he again joined with Sathyan Anthikkadu for
Kadha Thudarunnu. In 2011, he was featured in commercially successful films like
Makeup Man, along with comedic roles in
Seniors and
Chinatown and also
Swapna Sanchari. He then acted in films such as
Aadupuliyattam (2016) and
Pattabhiraman (2019). He played an important role Azhwarkkadiyan Nambi alias Thirumala in
Mani Ratnam historical action adventure
Ponniyin Selvan: I (2022) and
Ponniyin Selvan: II (2023). In the beginning of 2024 Jayaram had made an official comeback to Malayalam Cinema as hero in Abraham Ozler directed by Midhun Manuel Thomas. The movie is about a Veteran cop Abraham Ozler begins to investigate a mysterious unsolved case and the hunt for a serial killer begins. The movie also stars Mammootty in an extended cameo role. Abraham Ozler received mixed reviews from critics and the film made a total collection of ₹40.05 crore from the worldwide box office in first 30 days of its release and also emerged as the all-time highest grossing solo film in the career of its leading man Jayaram within its lifetime run at the theatres. The end of the film hints a sequel and Jayaram after the success of the film confirmed Abraham Ozler 2. ==Personal life==